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Gregory D. Sides - One of the best experts on this subject based on the ideXlab platform.

  • comparative efficacy of 5 days of Dirithromycin and 7 days of erythromycin in skin and soft tissue infections
    Journal of Antimicrobial Chemotherapy, 2000
    Co-Authors: Margaret M Wasilewski, Gregory D. Sides, Michael G Wilson, Jennifer L Stotka
    Abstract:

    We investigated the comparative efficacy and safety of Dirithromycin and erythromycin in the treatment of skin and soft tissue infections in this double-blind, randomized, multicentre study, in which 439 patients were randomized to treatment with Dirithromycin (500 mg daily for 5 days) or erythromycin (250 mg every 6 h for 7 days). All randomized patients were included in the termination analysis, which showed that 187 of 220 (85.0%) Dirithromycin recipients and 177 of 219 (80.8%) erythromycin recipients were clinically cured or improved (95% confidence interval (CI) � 3.0% to � 11.4%). In the termination analysis of the 211 bacteriologically evaluable patients, clinical cure or improvement occurred in 83 of 100 (83%) Dirithromycin recipients and in 89 of 111 (80.2%) erythromycin recipients (95% CI � 7.8% to � 13.4%), and bacteriological eradication occurred in 85 of 100 (85%) and 89 of 111 (80.2%), respectively. Adverse events were similar in incidence and nature between the two groups, except that there was less nausea with Dirithromycin (3.6% versus 8.2%; P � 0.042). Ten of 220 (4.5%) Dirithromycin recipients and 27 of 219 (12.3%) erythromycin recipients returned >20% of their prescribed medication (P � 0.033). In the treatment of skin and soft tissue infections, Dirithromycin (500 mg daily for 5 days) was comparable in efficacy to, and caused significantly less nausea than, erythromycin (250 mg every 6 h for 7 days). Compliance with the Dirithromycin regimen was superior to that with the erythromycin regimen.

  • five day Dirithromycin therapy is as effective as seven day erythromycin therapy for acute exacerbations of chronic bronchitis
    Journal of Antimicrobial Chemotherapy, 1999
    Co-Authors: Margaret M Wasilewski, Don Johns, Gregory D. Sides
    Abstract:

    In a meta-analysis of two identically designed, well-controlled, randomized, double-blind clinical trials, we compared 5 days of Dirithromycin with 7 days of erythromycin for acute exacerbations of chronic bronchitis. Five hundred and thirty-one patients were randomized to receive Dirithromycin (500 mg od) for 5 days and 526 patients were randomized to receive erythromycin (250 mg qid) for 7 days. Clinical and bacteriological responses were assessed 3-5 days after therapy and at termination from the study. Adverse events were collected from both groups and compared with each other, before and after treatment. Of the 690 patients clinically appraisable at the post-therapy visit, 298 (84.2%) Dirithromycin-treated patients and 270 (80.4%) erythromycin-treated patients showed a favourable response. At termination, 273 (77.1%) Dirithromycin-treated patients and 243 (72.3%) erythromycin-treated patients showed a favourable response. The microbiological cure was equivalent in the two groups (75% of Dirithromycin-treated patients and 74.1% of erythromycin-treated patients showed a favourable response at termination). After therapy, Dirithromycin was as effective as erythromycin in eradicating Streptococcus pneumoniae (77.8% vs 90.9%), Haemophilus influenzae (71.7% vs 72.2%), Moraxella catarrhalis (93.3% vs 88.9%) and Staphylococcus aureus (81.8% vs 82.1%). Although not statistically significant, fewer Dirithromycin-treated patients reported adverse events than did erythromycin-treated patients. Nausea (6.8% vs 7.8%), headache (7.3% vs 8.2%) and diarrhoea (6.6% vs 9.5%) were the most frequently reported adverse events in both groups. In the treatment of acute exacerbations of chronic bronchitis, 5 days of Dirithromycin is as effective as 7 days of erythromycin.

  • comparison of Dirithromycin and penicillin for treatment of streptococcal pharyngitis
    Antimicrobial Agents and Chemotherapy, 1997
    Co-Authors: V S Watkins, Gregory D. Sides, Paul M Conforti, Maria G Smietana, W Huck
    Abstract:

    In the treatment of group A beta-hemolytic streptococcal pharyngitis, penicillin is the drug of choice and erythromycin is the alternative. In a double-blind, randomized study, Dirithromycin, a new macrolide, was compared with penicillin for the treatment of streptococcal pharyngitis. Of 121 patients who were treated with Dirithromycin, 96.7% manifested a favorable clinical response, and of 136 patients treated with penicillin, 94.2% manifested a favorable clinical response. Streptococci were eradicated from the pharynges of 85.3% of 116 Dirithromycin-treated patients and 82.5% of 126 penicillin-treated patients who returned for follow-up. There were no statistically significant differences in efficacy between the two groups. The incidence of abdominal symptoms was higher in Dirithromycin-treated patients. Being as efficacious as penicillin and having the advantages over erythromycin of once-daily dosing and the lack of drug interactions, Dirithromycin is an alternative to penicillin in the treatment of streptococcal pharyngitis for patients 12 years of age and older.

  • effect of Dirithromycin on human cyp3a in vitro and on pharmacokinetics and pharmacodynamics of terfenadine in vivo
    The Journal of Clinical Pharmacology, 1996
    Co-Authors: Mark J Goldberg, Gregory D. Sides, K A Desante, Benito J Cerimele, Barbara J Ring, Barbara L Hatcher, Steven A Wrighton
    Abstract:

    Terfenadine is metabolized by the cytochrome P-450 3A subfamily of enzymes (CYP3A). Certain macrolide antibiotic agents inhibit CYP3A and, when coadministered with terfenadine, result in a drug interaction. The authors compared the abilities of Dirithromycin (a new macrolide antibiotic agent), its major metabolite erythromycylamine, and the known CYP3A substrate terfenadine to inhibit CYP3A in vitro. The hydroxylation of midazolam in human liver microsomes was used as a probe for CYP3A activity. Dirithromycin and erythromycylamine were low affinity inhibitors of CYP3A (inhibitory binding affinities of 493 μmol/L and 701 μmol/L, respectively); conversely, terfenadine was a moderate affinity inhibitor (inhibitory binding affinity of 28 μmol/L). Based on these data, the authors tested the hypothesis that Dirithromycin would not interact with terfenadine in humans. Six healthy men received terfenadine alone (60 mg twice daily) for 8 days, after which Dirithromycin (500 mg once daily) was added to the terfenadine regimen for an additional 10 days. The pharmacokinetics of terfenadine (and its acid metabolite) and the QTc interval were measured during both treatments, and it was found that neither parameter was affected. In this study, Dirithromycin was found to have low affinity for human CYP3A in vitro, which is in accordance with the study's finding that in vivo Dirithromycin has no major effect on the metabolism of the CYP3A substrate terfenadine in humans.

  • clinical efficacy of Dirithromycin in patients with bacteremic pneumonia
    Clinical Therapeutics, 1996
    Co-Authors: Jesus M Hernandez, Gregory D. Sides, Paul M Conforti, Maria G Smietana
    Abstract:

    Dirithromycin is a new macrolide antimicrobial drug with a long half-life (44 hours) that reaches high tissue concentrations, thus permitting once-daily oral dosing and shorter courses of therapy. Soon after absorption, Dirithromycin enters the tissue so rapidly that serum concentrations are comparatively low. It could be hypothesized that these low serum levels could endanger the outcome in patients with bacteremic pneumonia. We reviewed the database on Dirithromycin pneumonia (consisting of 1108 patients randomized to receive Dirithromycin or erythromycin in two double-masked trials) to ascertain its efficacy in patients with community-acquired pneumonia and concomitant bacteremia. Fourteen (2.5%) of 555 Dirithromycin-treated patients and 10 (1.8%) of 553 erythromycin-treated patients had bacteremia. A favorable clinical response posttherapy was observed in 92.3% and 88.9% of these patients with a response assigned, respectively. Overall, favorable response rates were comparable between the two groups in the bacteremic subsets: patients with pneumococcal bacteremia, patients with nonbacteremic pneumococcal pneumonia, and all patients enrolled with acute pneumonia who had a posttherapy clinical response. In the treatment of patients with mild or moderate community-acquired pneumonia, including those with unsuspected and incidental bacteremia, Dirithromycin is an effective macrolide antimicrobial drug.

Timothy J. Sullivan - One of the best experts on this subject based on the ideXlab platform.

  • a study of the interaction between Dirithromycin and astemizole in healthy adults
    American Journal of Therapeutics, 1997
    Co-Authors: Kenneth Bachmann, Timothy J. Sullivan, James H. Reese, Luis Jauregui, Kristen Miller, Mary Scott, Jennifer Stotka, Jac Harris
    Abstract:

    : The effect of a standard regimen of Dirithromycin, a macrolide antibiotic, on the single-dose pharmacokinetics of the H (1) receptor blocker astemizole was evaluated in a sample of 18 healthy young adults (nine males and nine females). The study was conducted in a two-way cross-over fashion after the subjects had been randomly given either Dirithromycin (two 250 mg tablets) or placebo (two tablets) every morning for 10 days. On the morning of the fourth dose of either Dirithromycin or placebo each subject ingested a single 30-mg oral dose (three 10-mg tablets) of astemizole. The disposition kinetics of both astemizole and its major metabolite, N-desmethylastemizole, were characterized after measuring the concentrations of both analytes in the serum fraction of serial blood samples collected for 14 days after the astemizole dose. In addition, corrected QT (QT(c) ) intervals were estimated from electrocardiogram rhythm strips that were run 24 hours prior to the astemizole dose, 12 hours after the astemizole dose, and after the last treatment (Dirithromycin or placebo) dose in both study periods. Pharmacokinetic parameters that were measured for both astemizole and N-desmethylastemizole during each treatment were: C(max), t(max), AUC (0-infinity), CL(oral), half-life, and volume of distribution (V). None of the parameters for N-desmethylastemizole was different when comparing data by ANOVA from the Dirithromycin treatment period with that of the placebo treatment period. On the other hand, during Dirithromycin treatment astemizole CL(oral) was 34% slower, volume of distribution was 24% larger, and half-life was 84% longer. Generally, all QT ( c ) intervals did not appear to be affected by Dirithromycin treatment. The changes in astemizole kinetics could not be attributed to its N-demethylation since the dispositional kinetics of N-desmethylastemizole were unaffected by Dirithromycin. Therefore, it is difficult to ascertain the clinical significance of the changes in astemizole kinetics. Since there were no significant differences for mean QT(c) intervals and no effect of Dirithromycin treatment on N-desmethylastemizole kinetics, it is unlikely that a standard regimen of Dirithromycin would place a patient taking astemizole at an increased risk of torsade de pointes or related ventricular arrhythmias.

  • The Influence of Dirithromycin on the Pharmacokinetics of Cyclosporine in Healthy Subjects and in Renal Transplant Patients.
    American Journal of Therapeutics, 1995
    Co-Authors: Kenneth Bachmann, Timothy J. Sullivan, James H. Reese, Luis Jauregui, Kristen Miller, Mary Scott, Gregory D. Sides, Ronald S. Shapiro
    Abstract:

    : The effect of a standard regimen of the investigational macrolide antibiotic, Dirithromycin, on the single-dose kinetics of orally administered cyclosporine (CSA) was investigated in healthy young males and on the steady-state disposition kinetics of cyclosporine in a panel of renal transplant patients. Eight male volunteers participated after giving informed consent. CSA was administered in three single doses (15 mg kg(minus sign1) p.o. each) in each of three phases: (1) prior to a 14-day regimen of Dirithromycin; (2) at the end of a 14-day regimen of Dirithromycin (500 mg p.o. qAM); and (3) 2 weeks after the last dose of a 14-day regimen of Dirithromycin. Pharmacokinetic parameters of CSA were estimated, and the differences among treatments were assessed by analysis of variation. No significant differences among treatment (phase) means were detected (p < 0.05). We conclude that a typical 14-day regimen of Dirithromycin failed to alter the disposition kinetics of CSA when taken orally healthy young adult males. The effect of a standard regimen of Dirithromycin on the steady-state disposition kinetics of orally administered CSA was investigated in a panel of 15 stable renal transplant patients. Pharmacokinetic parameters for CSA were evaluated prior to, during, and 2 weeks after discontinuing a 14-day (500 mg day(minus sign1)) oral regimen of Dirithromycin. Dirithromycin elicited small but significant changes in the following parameters: C(av) was increased by 16% during Dirithromycin treatment, and the changes in normalized C(av) were comparable. Likewise, C(SS,min) and normalized C(SS,min) were increased by 19% and 20%, respectively, during Dirithromycin treatment. CSA oral clearance, CL/F(SS), decreased by 17% during Dirithromycin treatment. C(SS,max) and normalized C(SS,max) were increased by 13% and 17%, respectively, during Dirithromycin treatment but were not significantly different from those either before or after Dirithromycin. The magnitude of the pharmacokinetic changes for CSA during Dirithromycin treatment (

  • the influence of Dirithromycin on the pharmacokinetics of cyclosporine in healthy subjects and in renal transplant patients
    American Journal of Therapeutics, 1995
    Co-Authors: Kenneth Bachmann, Timothy J. Sullivan, James H. Reese, Luis Jauregui, Kristen Miller, Mary Scott, Gregory D. Sides, Ronald S. Shapiro
    Abstract:

    : The effect of a standard regimen of the investigational macrolide antibiotic, Dirithromycin, on the single-dose kinetics of orally administered cyclosporine (CSA) was investigated in healthy young males and on the steady-state disposition kinetics of cyclosporine in a panel of renal transplant patients. Eight male volunteers participated after giving informed consent. CSA was administered in three single doses (15 mg kg(minus sign1) p.o. each) in each of three phases: (1) prior to a 14-day regimen of Dirithromycin; (2) at the end of a 14-day regimen of Dirithromycin (500 mg p.o. qAM); and (3) 2 weeks after the last dose of a 14-day regimen of Dirithromycin. Pharmacokinetic parameters of CSA were estimated, and the differences among treatments were assessed by analysis of variation. No significant differences among treatment (phase) means were detected (p < 0.05). We conclude that a typical 14-day regimen of Dirithromycin failed to alter the disposition kinetics of CSA when taken orally healthy young adult males. The effect of a standard regimen of Dirithromycin on the steady-state disposition kinetics of orally administered CSA was investigated in a panel of 15 stable renal transplant patients. Pharmacokinetic parameters for CSA were evaluated prior to, during, and 2 weeks after discontinuing a 14-day (500 mg day(minus sign1)) oral regimen of Dirithromycin. Dirithromycin elicited small but significant changes in the following parameters: C(av) was increased by 16% during Dirithromycin treatment, and the changes in normalized C(av) were comparable. Likewise, C(SS,min) and normalized C(SS,min) were increased by 19% and 20%, respectively, during Dirithromycin treatment. CSA oral clearance, CL/F(SS), decreased by 17% during Dirithromycin treatment. C(SS,max) and normalized C(SS,max) were increased by 13% and 17%, respectively, during Dirithromycin treatment but were not significantly different from those either before or after Dirithromycin. The magnitude of the pharmacokinetic changes for CSA during Dirithromycin treatment (<15% in normal subjects and 15--20% in renal transplant patients) when considered in the context of the therapeutic range of cyclosporine concentrations was relatively small, and not likely to warrant special attention to the dosing of CSA in such patients beyond routine whole-blood CSA and serum creatinine monitoring.

  • steady state pharmacokinetics of theophylline in copd patients treated with Dirithromycin
    The Journal of Clinical Pharmacology, 1993
    Co-Authors: Kenneth Bachmann, Luis Jauregui, Gregory D. Sides, Timothy J. Sullivan
    Abstract:

    : Steady-state theophylline pharmacokinetic parameters were studied in a panel of 14 patients with chronic obstructive pulmonary disease (COPD). Pharmacokinetic parameters were evaluated before, during, and after a 10-day regimen of the macrolide antibiotic, Dirithromycin. The addition of Dirithromycin (500 mg orally once daily at 7:00 AM) to a sustained-release theophylline dosing regimen (every 12 hours) elicited small changes in the steady-state pharmacokinetics of theophylline, which were not statistically significant. Mean steady-state plasma theophylline trough concentrations (Css,min) were invariant before, during, and after Dirithromycin treatment. Mean average steady-state plasma theophylline concentrations (Cav) declined by 7% during Dirithromycin treatment (NS), and mean peak plasma concentrations (Css,max) declined by 12% (NS). Theophylline clearance (CL/F) also remained relatively unchanged during Dirithromycin treatment exhibiting an increase of only 11% (NS). Dirithromycin treatment does not significantly affect the steady-state pharmacokinetics of theophylline, and its use in COPD patients is not likely to modify treatment outcomes with theophylline.

  • Steady‐State Pharmacokinetics of Theophylline in COPD Patients Treated With Dirithromycin
    The Journal of Clinical Pharmacology, 1993
    Co-Authors: Kenneth Bachmann, Luis Jauregui, Gregory D. Sides, Timothy J. Sullivan
    Abstract:

    : Steady-state theophylline pharmacokinetic parameters were studied in a panel of 14 patients with chronic obstructive pulmonary disease (COPD). Pharmacokinetic parameters were evaluated before, during, and after a 10-day regimen of the macrolide antibiotic, Dirithromycin. The addition of Dirithromycin (500 mg orally once daily at 7:00 AM) to a sustained-release theophylline dosing regimen (every 12 hours) elicited small changes in the steady-state pharmacokinetics of theophylline, which were not statistically significant. Mean steady-state plasma theophylline trough concentrations (Css,min) were invariant before, during, and after Dirithromycin treatment. Mean average steady-state plasma theophylline concentrations (Cav) declined by 7% during Dirithromycin treatment (NS), and mean peak plasma concentrations (Css,max) declined by 12% (NS). Theophylline clearance (CL/F) also remained relatively unchanged during Dirithromycin treatment exhibiting an increase of only 11% (NS). Dirithromycin treatment does not significantly affect the steady-state pharmacokinetics of theophylline, and its use in COPD patients is not likely to modify treatment outcomes with theophylline.

Kenneth Bachmann - One of the best experts on this subject based on the ideXlab platform.

  • a study of the interaction between Dirithromycin and astemizole in healthy adults
    American Journal of Therapeutics, 1997
    Co-Authors: Kenneth Bachmann, Timothy J. Sullivan, James H. Reese, Luis Jauregui, Kristen Miller, Mary Scott, Jennifer Stotka, Jac Harris
    Abstract:

    : The effect of a standard regimen of Dirithromycin, a macrolide antibiotic, on the single-dose pharmacokinetics of the H (1) receptor blocker astemizole was evaluated in a sample of 18 healthy young adults (nine males and nine females). The study was conducted in a two-way cross-over fashion after the subjects had been randomly given either Dirithromycin (two 250 mg tablets) or placebo (two tablets) every morning for 10 days. On the morning of the fourth dose of either Dirithromycin or placebo each subject ingested a single 30-mg oral dose (three 10-mg tablets) of astemizole. The disposition kinetics of both astemizole and its major metabolite, N-desmethylastemizole, were characterized after measuring the concentrations of both analytes in the serum fraction of serial blood samples collected for 14 days after the astemizole dose. In addition, corrected QT (QT(c) ) intervals were estimated from electrocardiogram rhythm strips that were run 24 hours prior to the astemizole dose, 12 hours after the astemizole dose, and after the last treatment (Dirithromycin or placebo) dose in both study periods. Pharmacokinetic parameters that were measured for both astemizole and N-desmethylastemizole during each treatment were: C(max), t(max), AUC (0-infinity), CL(oral), half-life, and volume of distribution (V). None of the parameters for N-desmethylastemizole was different when comparing data by ANOVA from the Dirithromycin treatment period with that of the placebo treatment period. On the other hand, during Dirithromycin treatment astemizole CL(oral) was 34% slower, volume of distribution was 24% larger, and half-life was 84% longer. Generally, all QT ( c ) intervals did not appear to be affected by Dirithromycin treatment. The changes in astemizole kinetics could not be attributed to its N-demethylation since the dispositional kinetics of N-desmethylastemizole were unaffected by Dirithromycin. Therefore, it is difficult to ascertain the clinical significance of the changes in astemizole kinetics. Since there were no significant differences for mean QT(c) intervals and no effect of Dirithromycin treatment on N-desmethylastemizole kinetics, it is unlikely that a standard regimen of Dirithromycin would place a patient taking astemizole at an increased risk of torsade de pointes or related ventricular arrhythmias.

  • The Influence of Dirithromycin on the Pharmacokinetics of Cyclosporine in Healthy Subjects and in Renal Transplant Patients.
    American Journal of Therapeutics, 1995
    Co-Authors: Kenneth Bachmann, Timothy J. Sullivan, James H. Reese, Luis Jauregui, Kristen Miller, Mary Scott, Gregory D. Sides, Ronald S. Shapiro
    Abstract:

    : The effect of a standard regimen of the investigational macrolide antibiotic, Dirithromycin, on the single-dose kinetics of orally administered cyclosporine (CSA) was investigated in healthy young males and on the steady-state disposition kinetics of cyclosporine in a panel of renal transplant patients. Eight male volunteers participated after giving informed consent. CSA was administered in three single doses (15 mg kg(minus sign1) p.o. each) in each of three phases: (1) prior to a 14-day regimen of Dirithromycin; (2) at the end of a 14-day regimen of Dirithromycin (500 mg p.o. qAM); and (3) 2 weeks after the last dose of a 14-day regimen of Dirithromycin. Pharmacokinetic parameters of CSA were estimated, and the differences among treatments were assessed by analysis of variation. No significant differences among treatment (phase) means were detected (p < 0.05). We conclude that a typical 14-day regimen of Dirithromycin failed to alter the disposition kinetics of CSA when taken orally healthy young adult males. The effect of a standard regimen of Dirithromycin on the steady-state disposition kinetics of orally administered CSA was investigated in a panel of 15 stable renal transplant patients. Pharmacokinetic parameters for CSA were evaluated prior to, during, and 2 weeks after discontinuing a 14-day (500 mg day(minus sign1)) oral regimen of Dirithromycin. Dirithromycin elicited small but significant changes in the following parameters: C(av) was increased by 16% during Dirithromycin treatment, and the changes in normalized C(av) were comparable. Likewise, C(SS,min) and normalized C(SS,min) were increased by 19% and 20%, respectively, during Dirithromycin treatment. CSA oral clearance, CL/F(SS), decreased by 17% during Dirithromycin treatment. C(SS,max) and normalized C(SS,max) were increased by 13% and 17%, respectively, during Dirithromycin treatment but were not significantly different from those either before or after Dirithromycin. The magnitude of the pharmacokinetic changes for CSA during Dirithromycin treatment (

  • the influence of Dirithromycin on the pharmacokinetics of cyclosporine in healthy subjects and in renal transplant patients
    American Journal of Therapeutics, 1995
    Co-Authors: Kenneth Bachmann, Timothy J. Sullivan, James H. Reese, Luis Jauregui, Kristen Miller, Mary Scott, Gregory D. Sides, Ronald S. Shapiro
    Abstract:

    : The effect of a standard regimen of the investigational macrolide antibiotic, Dirithromycin, on the single-dose kinetics of orally administered cyclosporine (CSA) was investigated in healthy young males and on the steady-state disposition kinetics of cyclosporine in a panel of renal transplant patients. Eight male volunteers participated after giving informed consent. CSA was administered in three single doses (15 mg kg(minus sign1) p.o. each) in each of three phases: (1) prior to a 14-day regimen of Dirithromycin; (2) at the end of a 14-day regimen of Dirithromycin (500 mg p.o. qAM); and (3) 2 weeks after the last dose of a 14-day regimen of Dirithromycin. Pharmacokinetic parameters of CSA were estimated, and the differences among treatments were assessed by analysis of variation. No significant differences among treatment (phase) means were detected (p < 0.05). We conclude that a typical 14-day regimen of Dirithromycin failed to alter the disposition kinetics of CSA when taken orally healthy young adult males. The effect of a standard regimen of Dirithromycin on the steady-state disposition kinetics of orally administered CSA was investigated in a panel of 15 stable renal transplant patients. Pharmacokinetic parameters for CSA were evaluated prior to, during, and 2 weeks after discontinuing a 14-day (500 mg day(minus sign1)) oral regimen of Dirithromycin. Dirithromycin elicited small but significant changes in the following parameters: C(av) was increased by 16% during Dirithromycin treatment, and the changes in normalized C(av) were comparable. Likewise, C(SS,min) and normalized C(SS,min) were increased by 19% and 20%, respectively, during Dirithromycin treatment. CSA oral clearance, CL/F(SS), decreased by 17% during Dirithromycin treatment. C(SS,max) and normalized C(SS,max) were increased by 13% and 17%, respectively, during Dirithromycin treatment but were not significantly different from those either before or after Dirithromycin. The magnitude of the pharmacokinetic changes for CSA during Dirithromycin treatment (<15% in normal subjects and 15--20% in renal transplant patients) when considered in the context of the therapeutic range of cyclosporine concentrations was relatively small, and not likely to warrant special attention to the dosing of CSA in such patients beyond routine whole-blood CSA and serum creatinine monitoring.

  • steady state pharmacokinetics of theophylline in copd patients treated with Dirithromycin
    The Journal of Clinical Pharmacology, 1993
    Co-Authors: Kenneth Bachmann, Luis Jauregui, Gregory D. Sides, Timothy J. Sullivan
    Abstract:

    : Steady-state theophylline pharmacokinetic parameters were studied in a panel of 14 patients with chronic obstructive pulmonary disease (COPD). Pharmacokinetic parameters were evaluated before, during, and after a 10-day regimen of the macrolide antibiotic, Dirithromycin. The addition of Dirithromycin (500 mg orally once daily at 7:00 AM) to a sustained-release theophylline dosing regimen (every 12 hours) elicited small changes in the steady-state pharmacokinetics of theophylline, which were not statistically significant. Mean steady-state plasma theophylline trough concentrations (Css,min) were invariant before, during, and after Dirithromycin treatment. Mean average steady-state plasma theophylline concentrations (Cav) declined by 7% during Dirithromycin treatment (NS), and mean peak plasma concentrations (Css,max) declined by 12% (NS). Theophylline clearance (CL/F) also remained relatively unchanged during Dirithromycin treatment exhibiting an increase of only 11% (NS). Dirithromycin treatment does not significantly affect the steady-state pharmacokinetics of theophylline, and its use in COPD patients is not likely to modify treatment outcomes with theophylline.

  • Steady‐State Pharmacokinetics of Theophylline in COPD Patients Treated With Dirithromycin
    The Journal of Clinical Pharmacology, 1993
    Co-Authors: Kenneth Bachmann, Luis Jauregui, Gregory D. Sides, Timothy J. Sullivan
    Abstract:

    : Steady-state theophylline pharmacokinetic parameters were studied in a panel of 14 patients with chronic obstructive pulmonary disease (COPD). Pharmacokinetic parameters were evaluated before, during, and after a 10-day regimen of the macrolide antibiotic, Dirithromycin. The addition of Dirithromycin (500 mg orally once daily at 7:00 AM) to a sustained-release theophylline dosing regimen (every 12 hours) elicited small changes in the steady-state pharmacokinetics of theophylline, which were not statistically significant. Mean steady-state plasma theophylline trough concentrations (Css,min) were invariant before, during, and after Dirithromycin treatment. Mean average steady-state plasma theophylline concentrations (Cav) declined by 7% during Dirithromycin treatment (NS), and mean peak plasma concentrations (Css,max) declined by 12% (NS). Theophylline clearance (CL/F) also remained relatively unchanged during Dirithromycin treatment exhibiting an increase of only 11% (NS). Dirithromycin treatment does not significantly affect the steady-state pharmacokinetics of theophylline, and its use in COPD patients is not likely to modify treatment outcomes with theophylline.

Paul M Conforti - One of the best experts on this subject based on the ideXlab platform.

  • comparison of Dirithromycin and penicillin for treatment of streptococcal pharyngitis
    Antimicrobial Agents and Chemotherapy, 1997
    Co-Authors: V S Watkins, Gregory D. Sides, Paul M Conforti, Maria G Smietana, W Huck
    Abstract:

    In the treatment of group A beta-hemolytic streptococcal pharyngitis, penicillin is the drug of choice and erythromycin is the alternative. In a double-blind, randomized study, Dirithromycin, a new macrolide, was compared with penicillin for the treatment of streptococcal pharyngitis. Of 121 patients who were treated with Dirithromycin, 96.7% manifested a favorable clinical response, and of 136 patients treated with penicillin, 94.2% manifested a favorable clinical response. Streptococci were eradicated from the pharynges of 85.3% of 116 Dirithromycin-treated patients and 82.5% of 126 penicillin-treated patients who returned for follow-up. There were no statistically significant differences in efficacy between the two groups. The incidence of abdominal symptoms was higher in Dirithromycin-treated patients. Being as efficacious as penicillin and having the advantages over erythromycin of once-daily dosing and the lack of drug interactions, Dirithromycin is an alternative to penicillin in the treatment of streptococcal pharyngitis for patients 12 years of age and older.

  • clinical efficacy of Dirithromycin in patients with bacteremic pneumonia
    Clinical Therapeutics, 1996
    Co-Authors: Jesus M Hernandez, Gregory D. Sides, Paul M Conforti, Maria G Smietana
    Abstract:

    Dirithromycin is a new macrolide antimicrobial drug with a long half-life (44 hours) that reaches high tissue concentrations, thus permitting once-daily oral dosing and shorter courses of therapy. Soon after absorption, Dirithromycin enters the tissue so rapidly that serum concentrations are comparatively low. It could be hypothesized that these low serum levels could endanger the outcome in patients with bacteremic pneumonia. We reviewed the database on Dirithromycin pneumonia (consisting of 1108 patients randomized to receive Dirithromycin or erythromycin in two double-masked trials) to ascertain its efficacy in patients with community-acquired pneumonia and concomitant bacteremia. Fourteen (2.5%) of 555 Dirithromycin-treated patients and 10 (1.8%) of 553 erythromycin-treated patients had bacteremia. A favorable clinical response posttherapy was observed in 92.3% and 88.9% of these patients with a response assigned, respectively. Overall, favorable response rates were comparable between the two groups in the bacteremic subsets: patients with pneumococcal bacteremia, patients with nonbacteremic pneumococcal pneumonia, and all patients enrolled with acute pneumonia who had a posttherapy clinical response. In the treatment of patients with mild or moderate community-acquired pneumonia, including those with unsuspected and incidental bacteremia, Dirithromycin is an effective macrolide antimicrobial drug.

  • tonsillar tissue penetration of Dirithromycin after multiple doses
    The Journal of Clinical Pharmacology, 1996
    Co-Authors: John M Benson, Gregory D. Sides, Paul M Conforti, James E Arnold, Scott C Manning, Dennis L Coleman, Eloise Lemon, Vish S Watkins
    Abstract:

    Dirithromycin is a new macrolide antibiotic that is effective against group A β-hemolytic streptococcal pharyngotonsillitis. This prospective, multicenter, randomized study compared the serum and tonsil tissue concentrations of erythromycylamine (to which Dirithromycin is rapidly converted by nonenzymatic hydrolysis during absorption) and erythromycin after 5- and 10-day regimens of Dirithromycin and erythromycin, respectively. Thirty-nine patients undergoing elective tonsillectomy but without active tonsillitis were assigned in randomized fashion to receive Dirithromycin 500 mg orally once daily (n = 22) or erythromycin base 250 mg orally four times daily (n = 17). Data from 12 patients receiving Dirithromycin and 10 receiving erythromycin were eligible for analysis. Mean serum concentrations (± standard deviation) of erythromycylamine and erythromycin were 0.20 ± 0.07 μg/mL and 0.12 ± 0.25 μg/mL, respectively, after the 5-day regimen and 0.17 ± 0.10 μg/mL and 1.57 ± 3.16 μg/mL, respectively, after the 10-day regimen. The mean serum concentration of erythromycin after 10 days was skewed by the data for one of the six patients in the group (concentration of >8 μg/mL). Mean concentrations of erythromycylamine in tonsil tissue were 4.62 ± 0.97 μg/g after 5 days and 3.47 ± 2.84 μg/g after 10 days. Concentrations in tonsillar tissue were undetectable in all patients given erythromycin for 5 days and in 4 of the 6 patients given erythromycin for 10 days. The high concentrations of erythromycylamine in tonsillar tissue agree with the clinical efficacy seen in the treatment of group A β-hemolytic streptococcal tonsillopharyngitis with Dirithromycin.

  • safety profile of Dirithromycin
    Journal of Antimicrobial Chemotherapy, 1993
    Co-Authors: Gregory D. Sides, Paul M Conforti
    Abstract:

    : Dirithromycin is a recently developed oral antibiotic, and has been shown to be effective in the treatment of respiratory tract, skin and soft tissue infections. Dirithromycin is administered once daily which may contribute to patient compliance. In this paper we review the data from studies conducted in Europe, USA, Israel and South Africa over a six-year period to assess the safety and efficacy of Dirithromycin in the treatment of a variety of acute infectious illnesses, and to compare it with structurally related antibiotics (erythromycin base, roxithromycin, and miocamycin) given orally. A total of 7437 patients have been enrolled from a total of 66 studies and trials, 4263 (57.3%) treated with Dirithromycin and 3174 (42.7%) treated with a comparator antibiotic. Patients received either 500 mg Dirithromycin (two tablets once daily), 1000 mg erythromycin base (250 mg qid), 300 mg roxithromycin (150 mg bid), or 1200 miocamycin (600 mg bid); the length of therapy ranged from 7 to 14 days. These studies have shown that Dirithromycin has a safety profile similar to the comparator agents. The most frequently reported adverse events for both Dirithromycin and comparator treatment groups were gastrointestinal in nature. The majority (99%) of adverse events reported from patients treated with Dirithromycin were considered mild or moderate in severity. Early discontinuation of antibiotic therapy was infrequent (3-4%) in both treatment groups, and considered to be possibly drug-related in 2-3% of the population. The safety profile of Dirithromycin in elderly patients was comparable to that recorded in the overall patient population. The incidence and nature of abnormal clinical laboratory evaluation were similar in Dirithromycin and comparator groups. Notable alterations in laboratory tests of haematological or hepatic function were infrequent and were not associated with clinical manifestations. Routine monitoring of standard clinical laboratory tests in patients prescribed Dirithromycin does not appear to be necessary.

  • Dirithromycin in the treatment of streptococcal pharyngitis
    Journal of Antimicrobial Chemotherapy, 1993
    Co-Authors: Martine Derriennic, Paul M Conforti, Gregory D. Sides
    Abstract:

    : A double-blind, double-dummy, randomized, multicentre study compared the safety and the efficacy of Dirithromycin (two 250 mg tablets, once daily) to erythromycin base (four 250 mg tablets, four times daily) for ten days in the treatment of proven group A beta-haemolytic (GABHs) streptococcal pharyngitis. Five-hundred and fifty-three patients (265 Dirithromycin, 288 erythromycin) were enrolled in the trial and analysed for efficacy and safety. Clinical and bacteriological evaluations were performed pre-therapy, during therapy (days 3-5), post-therapy (three to five days after completion of treatment), and late post-therapy (three to five weeks after treatment). All patients qualified for safety analysis. A negative pre-therapy culture was the predominant reason a patient did not qualify for analysis of efficacy. At post-therapy, favourable clinical responses (cure or improvement) were reported for 94.1% (159/169) of Dirithromycin and 94.6% (158/167) of erythromycin patients who qualified for efficacy analysis. Post-therapy throat cultures were negative for GABH streptococci in 79.3% (134/169) of Dirithromycin patients and 86.2% (144/167) of patients treated with erythromycin (P = 0.314). At late post-therapy 87.6% (134/153) of Dirithromycin and 88.7% (134/151) of erythromycin patients reported a favourable clinical response; pathogens were absent in 69.9% (107/153) of Dirithromycin and 86.1% (130/151) of erythromycin patients (P = 0.001). The adverse event profile of the two drugs was comparable although digestive and cutaneous adverse events were reported more frequently in the erythromycin treatment group. In this study, more Dirithromycin patients had throat cultures positive for GABH streptococci at late post-therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

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  • a study of the interaction between Dirithromycin and astemizole in healthy adults
    American Journal of Therapeutics, 1997
    Co-Authors: Kenneth Bachmann, Timothy J. Sullivan, James H. Reese, Luis Jauregui, Kristen Miller, Mary Scott, Jennifer Stotka, Jac Harris
    Abstract:

    : The effect of a standard regimen of Dirithromycin, a macrolide antibiotic, on the single-dose pharmacokinetics of the H (1) receptor blocker astemizole was evaluated in a sample of 18 healthy young adults (nine males and nine females). The study was conducted in a two-way cross-over fashion after the subjects had been randomly given either Dirithromycin (two 250 mg tablets) or placebo (two tablets) every morning for 10 days. On the morning of the fourth dose of either Dirithromycin or placebo each subject ingested a single 30-mg oral dose (three 10-mg tablets) of astemizole. The disposition kinetics of both astemizole and its major metabolite, N-desmethylastemizole, were characterized after measuring the concentrations of both analytes in the serum fraction of serial blood samples collected for 14 days after the astemizole dose. In addition, corrected QT (QT(c) ) intervals were estimated from electrocardiogram rhythm strips that were run 24 hours prior to the astemizole dose, 12 hours after the astemizole dose, and after the last treatment (Dirithromycin or placebo) dose in both study periods. Pharmacokinetic parameters that were measured for both astemizole and N-desmethylastemizole during each treatment were: C(max), t(max), AUC (0-infinity), CL(oral), half-life, and volume of distribution (V). None of the parameters for N-desmethylastemizole was different when comparing data by ANOVA from the Dirithromycin treatment period with that of the placebo treatment period. On the other hand, during Dirithromycin treatment astemizole CL(oral) was 34% slower, volume of distribution was 24% larger, and half-life was 84% longer. Generally, all QT ( c ) intervals did not appear to be affected by Dirithromycin treatment. The changes in astemizole kinetics could not be attributed to its N-demethylation since the dispositional kinetics of N-desmethylastemizole were unaffected by Dirithromycin. Therefore, it is difficult to ascertain the clinical significance of the changes in astemizole kinetics. Since there were no significant differences for mean QT(c) intervals and no effect of Dirithromycin treatment on N-desmethylastemizole kinetics, it is unlikely that a standard regimen of Dirithromycin would place a patient taking astemizole at an increased risk of torsade de pointes or related ventricular arrhythmias.

  • The Influence of Dirithromycin on the Pharmacokinetics of Cyclosporine in Healthy Subjects and in Renal Transplant Patients.
    American Journal of Therapeutics, 1995
    Co-Authors: Kenneth Bachmann, Timothy J. Sullivan, James H. Reese, Luis Jauregui, Kristen Miller, Mary Scott, Gregory D. Sides, Ronald S. Shapiro
    Abstract:

    : The effect of a standard regimen of the investigational macrolide antibiotic, Dirithromycin, on the single-dose kinetics of orally administered cyclosporine (CSA) was investigated in healthy young males and on the steady-state disposition kinetics of cyclosporine in a panel of renal transplant patients. Eight male volunteers participated after giving informed consent. CSA was administered in three single doses (15 mg kg(minus sign1) p.o. each) in each of three phases: (1) prior to a 14-day regimen of Dirithromycin; (2) at the end of a 14-day regimen of Dirithromycin (500 mg p.o. qAM); and (3) 2 weeks after the last dose of a 14-day regimen of Dirithromycin. Pharmacokinetic parameters of CSA were estimated, and the differences among treatments were assessed by analysis of variation. No significant differences among treatment (phase) means were detected (p < 0.05). We conclude that a typical 14-day regimen of Dirithromycin failed to alter the disposition kinetics of CSA when taken orally healthy young adult males. The effect of a standard regimen of Dirithromycin on the steady-state disposition kinetics of orally administered CSA was investigated in a panel of 15 stable renal transplant patients. Pharmacokinetic parameters for CSA were evaluated prior to, during, and 2 weeks after discontinuing a 14-day (500 mg day(minus sign1)) oral regimen of Dirithromycin. Dirithromycin elicited small but significant changes in the following parameters: C(av) was increased by 16% during Dirithromycin treatment, and the changes in normalized C(av) were comparable. Likewise, C(SS,min) and normalized C(SS,min) were increased by 19% and 20%, respectively, during Dirithromycin treatment. CSA oral clearance, CL/F(SS), decreased by 17% during Dirithromycin treatment. C(SS,max) and normalized C(SS,max) were increased by 13% and 17%, respectively, during Dirithromycin treatment but were not significantly different from those either before or after Dirithromycin. The magnitude of the pharmacokinetic changes for CSA during Dirithromycin treatment (

  • the influence of Dirithromycin on the pharmacokinetics of cyclosporine in healthy subjects and in renal transplant patients
    American Journal of Therapeutics, 1995
    Co-Authors: Kenneth Bachmann, Timothy J. Sullivan, James H. Reese, Luis Jauregui, Kristen Miller, Mary Scott, Gregory D. Sides, Ronald S. Shapiro
    Abstract:

    : The effect of a standard regimen of the investigational macrolide antibiotic, Dirithromycin, on the single-dose kinetics of orally administered cyclosporine (CSA) was investigated in healthy young males and on the steady-state disposition kinetics of cyclosporine in a panel of renal transplant patients. Eight male volunteers participated after giving informed consent. CSA was administered in three single doses (15 mg kg(minus sign1) p.o. each) in each of three phases: (1) prior to a 14-day regimen of Dirithromycin; (2) at the end of a 14-day regimen of Dirithromycin (500 mg p.o. qAM); and (3) 2 weeks after the last dose of a 14-day regimen of Dirithromycin. Pharmacokinetic parameters of CSA were estimated, and the differences among treatments were assessed by analysis of variation. No significant differences among treatment (phase) means were detected (p < 0.05). We conclude that a typical 14-day regimen of Dirithromycin failed to alter the disposition kinetics of CSA when taken orally healthy young adult males. The effect of a standard regimen of Dirithromycin on the steady-state disposition kinetics of orally administered CSA was investigated in a panel of 15 stable renal transplant patients. Pharmacokinetic parameters for CSA were evaluated prior to, during, and 2 weeks after discontinuing a 14-day (500 mg day(minus sign1)) oral regimen of Dirithromycin. Dirithromycin elicited small but significant changes in the following parameters: C(av) was increased by 16% during Dirithromycin treatment, and the changes in normalized C(av) were comparable. Likewise, C(SS,min) and normalized C(SS,min) were increased by 19% and 20%, respectively, during Dirithromycin treatment. CSA oral clearance, CL/F(SS), decreased by 17% during Dirithromycin treatment. C(SS,max) and normalized C(SS,max) were increased by 13% and 17%, respectively, during Dirithromycin treatment but were not significantly different from those either before or after Dirithromycin. The magnitude of the pharmacokinetic changes for CSA during Dirithromycin treatment (<15% in normal subjects and 15--20% in renal transplant patients) when considered in the context of the therapeutic range of cyclosporine concentrations was relatively small, and not likely to warrant special attention to the dosing of CSA in such patients beyond routine whole-blood CSA and serum creatinine monitoring.

  • steady state pharmacokinetics of theophylline in copd patients treated with Dirithromycin
    The Journal of Clinical Pharmacology, 1993
    Co-Authors: Kenneth Bachmann, Luis Jauregui, Gregory D. Sides, Timothy J. Sullivan
    Abstract:

    : Steady-state theophylline pharmacokinetic parameters were studied in a panel of 14 patients with chronic obstructive pulmonary disease (COPD). Pharmacokinetic parameters were evaluated before, during, and after a 10-day regimen of the macrolide antibiotic, Dirithromycin. The addition of Dirithromycin (500 mg orally once daily at 7:00 AM) to a sustained-release theophylline dosing regimen (every 12 hours) elicited small changes in the steady-state pharmacokinetics of theophylline, which were not statistically significant. Mean steady-state plasma theophylline trough concentrations (Css,min) were invariant before, during, and after Dirithromycin treatment. Mean average steady-state plasma theophylline concentrations (Cav) declined by 7% during Dirithromycin treatment (NS), and mean peak plasma concentrations (Css,max) declined by 12% (NS). Theophylline clearance (CL/F) also remained relatively unchanged during Dirithromycin treatment exhibiting an increase of only 11% (NS). Dirithromycin treatment does not significantly affect the steady-state pharmacokinetics of theophylline, and its use in COPD patients is not likely to modify treatment outcomes with theophylline.

  • Steady‐State Pharmacokinetics of Theophylline in COPD Patients Treated With Dirithromycin
    The Journal of Clinical Pharmacology, 1993
    Co-Authors: Kenneth Bachmann, Luis Jauregui, Gregory D. Sides, Timothy J. Sullivan
    Abstract:

    : Steady-state theophylline pharmacokinetic parameters were studied in a panel of 14 patients with chronic obstructive pulmonary disease (COPD). Pharmacokinetic parameters were evaluated before, during, and after a 10-day regimen of the macrolide antibiotic, Dirithromycin. The addition of Dirithromycin (500 mg orally once daily at 7:00 AM) to a sustained-release theophylline dosing regimen (every 12 hours) elicited small changes in the steady-state pharmacokinetics of theophylline, which were not statistically significant. Mean steady-state plasma theophylline trough concentrations (Css,min) were invariant before, during, and after Dirithromycin treatment. Mean average steady-state plasma theophylline concentrations (Cav) declined by 7% during Dirithromycin treatment (NS), and mean peak plasma concentrations (Css,max) declined by 12% (NS). Theophylline clearance (CL/F) also remained relatively unchanged during Dirithromycin treatment exhibiting an increase of only 11% (NS). Dirithromycin treatment does not significantly affect the steady-state pharmacokinetics of theophylline, and its use in COPD patients is not likely to modify treatment outcomes with theophylline.