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R. B. Wilber - One of the best experts on this subject based on the ideXlab platform.

  • penetration of Cefprozil into tonsillar and adenoidal tissues
    Antimicrobial Agents and Chemotherapy, 1993
    Co-Authors: Wen Chyi Shyu, R. B. Wilber, J Reilly, D A Campbell, Rashmi H. Barbhaiya
    Abstract:

    Penetration of Cefprozil into tonsillar and/or adenoidal tissues was investigated for patients undergoing tonsillectomy and/or adenoidectomy. A total of 29 patients ranging in age from 2 to 14 years participated in the study. The tonsils and/or the adenoids were removed at times ranging from 0.33 to 3.17 h after oral administration of a dose of either 7.5 or 20 mg/kg of body weight. A blood sample was also collected as soon as the tissue sample was removed. Plasma, tonsil, and adenoid samples were analyzed for cis and trans isomers of Cefprozil by high-performance liquid chromatographic assays. The concentrations of the cis isomer of Cefprozil in plasma ranged from 0.60 to 9.87 micrograms/ml at the 7.5-mg/kg dose level and from 1.04 to 20.40 micrograms/ml at the 20-mg/kg dose level. The corresponding concentrations of the cis isomer in tonsil tissue ranged from 0.48 to 2.42 micrograms/g and from 1.00 to 4.29 micrograms/g, respectively. The corresponding concentrations of the cis isomer in adenoid tissue ranged from 0.40 to 4.20 micrograms/g and from 1.74 to 4.94 micrograms/g, respectively. The concentrations of the trans isomer were about 1/10 of those observed for the cis isomer. The median ratios of the Cefprozil concentration in tonsillar tissue to that in plasma were 0.37 and 0.47 for patients receiving a 7.5- or a 20-mg/kg oral dose of Cefprozil, respectively. The corresponding median ratios for the adenoidal tissue were 0.46 and 0.82, respectively. The Cefprozil concentrations in either the tonsillar or the adenoidal tissue at both dose levels over 3.17 h after dosing are much higher than the MICs for common pathogens which cause pharyngitis or tonsillitis.

  • oral absolute bioavailability and intravenous dose proportionality of Cefprozil in humans
    The Journal of Clinical Pharmacology, 1992
    Co-Authors: Wen Chyi Shyu, R. B. Wilber, K A Pittman, D A Campbell, Vinod R Shah, Rashmi H. Barbhaiya
    Abstract:

    : The absolute bioavailability (F) and dose proportionality of Cefprozil were investigated in a parallel design study with an embedded two-way crossover leg. Twenty-four healthy male subjects divided into 3 dosing groups received a single 250-, 500-, or 1000-mg dose of Cefprozil by a 30-minute intravenous infusion. Subjects assigned to the 500-mg dose group also received a 500-mg oral dose of Cefprozil in crossover manner with a wash-out period of 7 days between each treatment. Cefprozil consists of cis and trans isomers in an approximate 90:10 ratio. Serial blood and urine samples were collected and analyzed for the concentrations of the cis and trans isomers of the cephalosporin using high-pressure liquid chromatographic assay with UV detection methods. After the 250-, 500-, and 1000-mg intravenous administration of Cefprozil, the peak concentrations were 13.2, 26.0, and 48.5 micrograms/mL, and area under the plasma concentration versus time profiles were 17.2, 31.4, and 58.1 micrograms.hour/mL, respectively, for the cis isomer increasing in a dose proportional manner. Total body clearance, renal clearance, and volume of distribution at steady state, adjusted for body weight, were not significantly different among all groups. Mean residence time, elimination half-life, and urinary recovery were invariant with the dose. Based on the plasma and urine data, the estimates of F were 89% and 94% for the cis isomer, respectively. The plasma concentrations of the trans isomer were about 1/10th of the cis isomer, and all parameters were similar to those observed for the cis isomer. In summary, Cefprozil exhibits linear pharmacokinetics and is essentially completely absorbed after oral administration.

  • safety profile of Cefprozil
    Clinical Infectious Diseases, 1992
    Co-Authors: R. B. Wilber, Susan Durham, Caroline A Doyle, Barbara J Conetta, Sidney S Degraw, Alexander Leigh
    Abstract:

    : The clinical and laboratory safety of Cefprozil was analyzed with data from 4,227 patients who received the drug in North American and European clinical efficacy trials. Of these patients, 3,016 adults and children received capsules or tablets, while 1,211 patients (mostly children) were treated with Cefprozil suspension. Cefprozil was used in single-daily or twice-daily dosing regimens for treatment of infections of the upper and lower respiratory tracts, sinuses, middle ear, urinary tract, and skin and skin structure. The incidence of adverse clinical events and laboratory abnormalities was similar to that associated with use of other oral cephalosporins. Gastrointestinal adverse effects were the predominant adverse clinical event, although the incidence of diarrhea with Cefprozil was much lower than that with cephalosporins that are less well absorbed. The data confirm the safety of Cefprozil in both adult and pediatric patients.

  • excretion of Cefprozil into human breast milk
    Antimicrobial Agents and Chemotherapy, 1992
    Co-Authors: Wen Chyi Shyu, R. B. Wilber, K A Pittman, D A Campbell, Vinod R Shah, J Venitz, V Jaganathan, Rashmi H. Barbhaiya
    Abstract:

    The excretion of Cefprozil into breast milk in nine healthy, lactating female subjects was investigated. Each subject received a single 1,000-mg oral dose of Cefprozil consisting of cis and trans isomers in an approximately 90:10 ratio. Serial blood, urine, and breast milk samples were collected and analyzed for the concentrations of the cis and trans isomers by a specific high-pressure liquid chromatography-UV assay. The mean pharmacokinetic parameters for both isomers were essentially the same. The mean peak concentrations in plasma for the cis isomer were 14.8 micrograms/ml, and the area under the concentration curve was 54.8 micrograms.h/ml. The mean values of elimination half-life, renal clearance, and urinary excretion for the cis isomer were 1.69 h, 164 ml/min, and 60%, respectively. The mean concentrations in milk of the cis isomer over a 24-h period ranged from 0.25 to 3.36 micrograms/ml, with the maximum concentration appearing at 6 h after dosing. The average maximum concentration in milk of the trans isomer was less than 0.26 micrograms/ml. The concentrations of the trans isomer in plasma and in breast milk were about 1/10 of those for the cis isomer. Less than 0.3% of the dose was excreted in breast milk for both isomers of Cefprozil. Even if one assumes that the concentration of Cefprozil in milk remains constant at 3.36 micrograms/ml (the highest concentration of Cefprozil observed in breast milk), an infant ingesting an average of 800 ml of milk per day will be exposed to a maximum amount of about 3 mg of Cefprozil per day. This value represents about 0.3% of the maternal dose. Low excretion of Cefprozil in breast milk and the excellent safety profile of Cefprozil suggest that this cephalosporin may be administered to nursing mothers when indicated.

  • Cefprozil versus cefaclor in the treatment of mild to moderate skin and skin structure infections the Cefprozil multicenter study group
    Clinical Therapeutics, 1992
    Co-Authors: L C Parish, C A Doyle, S J Durham, R. B. Wilber
    Abstract:

    Abstract In a multicenter study, 598 patients with skin or skin-structure infections were randomly assigned to receive 500 mg of Cefprozil once daily (or 20 mg/kg once daily) or 250 mg of cefaclor three times daily (or 20 mg/kg daily in three equal doses) for 5 to 10 days. Treatment was evaluated in 212 Cefprozil-treated patients and in 210 cefaclor-treated patients. The patients were aged 2 to 99 years (mean, 28 years) and their primary diagnoses were impetigo (in 99 patients), pyoderma (in 98), superficial abscess (in 70), and cellulitis (in 64). A satisfactory clinical response was found in 93% of the Cefprozil-treated patients and in 92% of the cefaclor-treated patients, the pathogens were eradicated in 91% and 89%, and overall treatment was rated effective in 87% of both groups. Adverse clinical events were reported by 5% of the patients in both groups; one Cefprozil-treated patient and three cefaclor-treated patients withdrew from treatment because of adverse events. It is concluded that Cefprozil administered once daily is as effective and safe as cefaclor administered three times daily in the treatment of mild to moderate skin and skin-structure infections.

Rashmi H. Barbhaiya - One of the best experts on this subject based on the ideXlab platform.

  • penetration of Cefprozil into middle ear fluid of patients with otitis media
    Antimicrobial Agents and Chemotherapy, 1994
    Co-Authors: Wen Chyi Shyu, J Haddad, J Reilly, W N Khan, D A Campbell, Y H Tsai, Rashmi H. Barbhaiya
    Abstract:

    Penetration of Cefprozil into the middle ear fluid was investigated in patients with chronic otitis media. A total of 89 patients ranging from 7 months to 11 years old participated in the study. The middle ear fluid was removed by ventilation tubes inserted through the tympanic membrane at times ranging from 0.38 to 5.97 h after oral administration of a single dose of 15 or 20 mg/kg of body weight. A blood sample was also collected as soon as the middle ear fluid was removed. Plasma samples were analyzed for the concentration of Cefprozil by a high-performance liquid chromatographic assay. Middle ear fluid samples were analyzed for the concentration of Cefprozil by a microbiological assay. The concentrations of Cefprozil in plasma ranged from 0.38 to 15.97 micrograms/ml at the 15-mg/kg dose level and from 1.28 to 21.47 micrograms/ml at the 20-mg/kg dose level. The corresponding middle ear fluid concentrations of Cefprozil ranged from 0.06 to 4.44 micrograms/ml and from 0.17 to 8.67 micrograms/ml, respectively. Cefprozil penetrates well into middle ear fluid in patients with chronic otitis media.

  • Effects of Time of Administration and Posture on the Pharmacokinetics of Cefprozil
    Clinical Pharmacokinetics, 1993
    Co-Authors: Wen Chyi Shyu, Carol R. Gleason, Rashmi H. Barbhaiya
    Abstract:

    The effects of time of administration, sleep and posture on the pharmacokinetics of Cefprozil were evaluated in a single-dose 3-way crossover study. After a 6-hour fast, 12 healthy male volunteers received oral Cefprozil 250mg at 1200h (treatment A), 1200h (treatment B) and 2400h (treatment C) with a 7-day washout interval between each treatment. During the study period, volunteers receiving treatment A remained in a sitting/standing position or were ambulatory, those receiving treatment B were in the supine position, and those receiving treatment C were sleeping. Blood samples were taken over an 8-hour period and the plasma samples were analysed for the concentrations of Cefprozil by a high performance liquid chromatography-ultraviolet method. Plasma concentration vs time data were analysed using noncompartmental analysis methods. Mean peak plasma concentrations (C_max) were 4.51, 5.02 and 4.91 mg/L for treatments A, B and C, respectively. Corresponding mean values of the area under the plasma concentration-time curve (AUC_(0−∞)) were 12.6, 12.6 and 14.2 mg/L•h, respectively. The mean half-life (t_½) values were 1.30, 1.23 and 1.50 hours for treatments A, B and C, respectively. Mean AUC_(0−∞), C_max and t½ values following treatment B were not significantly different from those of treatment A. However, the mean AUC_(0−∞) and t_½ values of Cefprozil following treatment C were significantly greater than those of either treatment A or B. The mean C_max value following treatment C was not significantly different than that of either treatments A or B. From these results, it was concluded that posture has no effect on the pharmacokinetics of Cefprozil. The administration of Cefprozil at night decreases the rate of elimination and thereby increases total exposure to Cefprozil. However, the magnitude of the changes in these 2 parameters may not be of any clinical relevance.

  • Effects of Time of Administration and Posture on the Pharmacokinetics of Cefprozil
    Clinical Pharmacokinectics, 1993
    Co-Authors: Wen Chyi Shyu, Carol Gleason, Rashmi H. Barbhaiya
    Abstract:

    The effects of time of administration, sleep and posture on the pharmacokinetics of Cefprozil were evaluated in a single-dose 3-way crossover study. After a 6-hour fast, 12 healthy male volunteers received oral Cefprozil 250mg at 1200h (treatment A), 1200h (treatment B) and 2400h (treatment C) with a 7-day washout interval between each treatment. During the study period, volunteers receiving treatment A remained in a sitting/standing position or were ambulatory, those receiving treatment B were in the supine position, and those receiving treatment C were sleeping. Blood samples were taken over an 8-hour period and the plasma samples were analysed for the concentrations of Cefprozil by a high performance liquid chromatography-ultraviolet method. Plasma concentration vs time data were analysed using noncompartmental analysis methods.

  • penetration of Cefprozil into tonsillar and adenoidal tissues
    Antimicrobial Agents and Chemotherapy, 1993
    Co-Authors: Wen Chyi Shyu, R. B. Wilber, J Reilly, D A Campbell, Rashmi H. Barbhaiya
    Abstract:

    Penetration of Cefprozil into tonsillar and/or adenoidal tissues was investigated for patients undergoing tonsillectomy and/or adenoidectomy. A total of 29 patients ranging in age from 2 to 14 years participated in the study. The tonsils and/or the adenoids were removed at times ranging from 0.33 to 3.17 h after oral administration of a dose of either 7.5 or 20 mg/kg of body weight. A blood sample was also collected as soon as the tissue sample was removed. Plasma, tonsil, and adenoid samples were analyzed for cis and trans isomers of Cefprozil by high-performance liquid chromatographic assays. The concentrations of the cis isomer of Cefprozil in plasma ranged from 0.60 to 9.87 micrograms/ml at the 7.5-mg/kg dose level and from 1.04 to 20.40 micrograms/ml at the 20-mg/kg dose level. The corresponding concentrations of the cis isomer in tonsil tissue ranged from 0.48 to 2.42 micrograms/g and from 1.00 to 4.29 micrograms/g, respectively. The corresponding concentrations of the cis isomer in adenoid tissue ranged from 0.40 to 4.20 micrograms/g and from 1.74 to 4.94 micrograms/g, respectively. The concentrations of the trans isomer were about 1/10 of those observed for the cis isomer. The median ratios of the Cefprozil concentration in tonsillar tissue to that in plasma were 0.37 and 0.47 for patients receiving a 7.5- or a 20-mg/kg oral dose of Cefprozil, respectively. The corresponding median ratios for the adenoidal tissue were 0.46 and 0.82, respectively. The Cefprozil concentrations in either the tonsillar or the adenoidal tissue at both dose levels over 3.17 h after dosing are much higher than the MICs for common pathogens which cause pharyngitis or tonsillitis.

  • oral absolute bioavailability and intravenous dose proportionality of Cefprozil in humans
    The Journal of Clinical Pharmacology, 1992
    Co-Authors: Wen Chyi Shyu, R. B. Wilber, K A Pittman, D A Campbell, Vinod R Shah, Rashmi H. Barbhaiya
    Abstract:

    : The absolute bioavailability (F) and dose proportionality of Cefprozil were investigated in a parallel design study with an embedded two-way crossover leg. Twenty-four healthy male subjects divided into 3 dosing groups received a single 250-, 500-, or 1000-mg dose of Cefprozil by a 30-minute intravenous infusion. Subjects assigned to the 500-mg dose group also received a 500-mg oral dose of Cefprozil in crossover manner with a wash-out period of 7 days between each treatment. Cefprozil consists of cis and trans isomers in an approximate 90:10 ratio. Serial blood and urine samples were collected and analyzed for the concentrations of the cis and trans isomers of the cephalosporin using high-pressure liquid chromatographic assay with UV detection methods. After the 250-, 500-, and 1000-mg intravenous administration of Cefprozil, the peak concentrations were 13.2, 26.0, and 48.5 micrograms/mL, and area under the plasma concentration versus time profiles were 17.2, 31.4, and 58.1 micrograms.hour/mL, respectively, for the cis isomer increasing in a dose proportional manner. Total body clearance, renal clearance, and volume of distribution at steady state, adjusted for body weight, were not significantly different among all groups. Mean residence time, elimination half-life, and urinary recovery were invariant with the dose. Based on the plasma and urine data, the estimates of F were 89% and 94% for the cis isomer, respectively. The plasma concentrations of the trans isomer were about 1/10th of the cis isomer, and all parameters were similar to those observed for the cis isomer. In summary, Cefprozil exhibits linear pharmacokinetics and is essentially completely absorbed after oral administration.

Wen Chyi Shyu - One of the best experts on this subject based on the ideXlab platform.

  • penetration of Cefprozil into middle ear fluid of patients with otitis media
    Antimicrobial Agents and Chemotherapy, 1994
    Co-Authors: Wen Chyi Shyu, J Haddad, J Reilly, W N Khan, D A Campbell, Y H Tsai, Rashmi H. Barbhaiya
    Abstract:

    Penetration of Cefprozil into the middle ear fluid was investigated in patients with chronic otitis media. A total of 89 patients ranging from 7 months to 11 years old participated in the study. The middle ear fluid was removed by ventilation tubes inserted through the tympanic membrane at times ranging from 0.38 to 5.97 h after oral administration of a single dose of 15 or 20 mg/kg of body weight. A blood sample was also collected as soon as the middle ear fluid was removed. Plasma samples were analyzed for the concentration of Cefprozil by a high-performance liquid chromatographic assay. Middle ear fluid samples were analyzed for the concentration of Cefprozil by a microbiological assay. The concentrations of Cefprozil in plasma ranged from 0.38 to 15.97 micrograms/ml at the 15-mg/kg dose level and from 1.28 to 21.47 micrograms/ml at the 20-mg/kg dose level. The corresponding middle ear fluid concentrations of Cefprozil ranged from 0.06 to 4.44 micrograms/ml and from 0.17 to 8.67 micrograms/ml, respectively. Cefprozil penetrates well into middle ear fluid in patients with chronic otitis media.

  • Effects of Time of Administration and Posture on the Pharmacokinetics of Cefprozil
    Clinical Pharmacokinetics, 1993
    Co-Authors: Wen Chyi Shyu, Carol R. Gleason, Rashmi H. Barbhaiya
    Abstract:

    The effects of time of administration, sleep and posture on the pharmacokinetics of Cefprozil were evaluated in a single-dose 3-way crossover study. After a 6-hour fast, 12 healthy male volunteers received oral Cefprozil 250mg at 1200h (treatment A), 1200h (treatment B) and 2400h (treatment C) with a 7-day washout interval between each treatment. During the study period, volunteers receiving treatment A remained in a sitting/standing position or were ambulatory, those receiving treatment B were in the supine position, and those receiving treatment C were sleeping. Blood samples were taken over an 8-hour period and the plasma samples were analysed for the concentrations of Cefprozil by a high performance liquid chromatography-ultraviolet method. Plasma concentration vs time data were analysed using noncompartmental analysis methods. Mean peak plasma concentrations (C_max) were 4.51, 5.02 and 4.91 mg/L for treatments A, B and C, respectively. Corresponding mean values of the area under the plasma concentration-time curve (AUC_(0−∞)) were 12.6, 12.6 and 14.2 mg/L•h, respectively. The mean half-life (t_½) values were 1.30, 1.23 and 1.50 hours for treatments A, B and C, respectively. Mean AUC_(0−∞), C_max and t½ values following treatment B were not significantly different from those of treatment A. However, the mean AUC_(0−∞) and t_½ values of Cefprozil following treatment C were significantly greater than those of either treatment A or B. The mean C_max value following treatment C was not significantly different than that of either treatments A or B. From these results, it was concluded that posture has no effect on the pharmacokinetics of Cefprozil. The administration of Cefprozil at night decreases the rate of elimination and thereby increases total exposure to Cefprozil. However, the magnitude of the changes in these 2 parameters may not be of any clinical relevance.

  • Effects of Time of Administration and Posture on the Pharmacokinetics of Cefprozil
    Clinical Pharmacokinectics, 1993
    Co-Authors: Wen Chyi Shyu, Carol Gleason, Rashmi H. Barbhaiya
    Abstract:

    The effects of time of administration, sleep and posture on the pharmacokinetics of Cefprozil were evaluated in a single-dose 3-way crossover study. After a 6-hour fast, 12 healthy male volunteers received oral Cefprozil 250mg at 1200h (treatment A), 1200h (treatment B) and 2400h (treatment C) with a 7-day washout interval between each treatment. During the study period, volunteers receiving treatment A remained in a sitting/standing position or were ambulatory, those receiving treatment B were in the supine position, and those receiving treatment C were sleeping. Blood samples were taken over an 8-hour period and the plasma samples were analysed for the concentrations of Cefprozil by a high performance liquid chromatography-ultraviolet method. Plasma concentration vs time data were analysed using noncompartmental analysis methods.

  • penetration of Cefprozil into tonsillar and adenoidal tissues
    Antimicrobial Agents and Chemotherapy, 1993
    Co-Authors: Wen Chyi Shyu, R. B. Wilber, J Reilly, D A Campbell, Rashmi H. Barbhaiya
    Abstract:

    Penetration of Cefprozil into tonsillar and/or adenoidal tissues was investigated for patients undergoing tonsillectomy and/or adenoidectomy. A total of 29 patients ranging in age from 2 to 14 years participated in the study. The tonsils and/or the adenoids were removed at times ranging from 0.33 to 3.17 h after oral administration of a dose of either 7.5 or 20 mg/kg of body weight. A blood sample was also collected as soon as the tissue sample was removed. Plasma, tonsil, and adenoid samples were analyzed for cis and trans isomers of Cefprozil by high-performance liquid chromatographic assays. The concentrations of the cis isomer of Cefprozil in plasma ranged from 0.60 to 9.87 micrograms/ml at the 7.5-mg/kg dose level and from 1.04 to 20.40 micrograms/ml at the 20-mg/kg dose level. The corresponding concentrations of the cis isomer in tonsil tissue ranged from 0.48 to 2.42 micrograms/g and from 1.00 to 4.29 micrograms/g, respectively. The corresponding concentrations of the cis isomer in adenoid tissue ranged from 0.40 to 4.20 micrograms/g and from 1.74 to 4.94 micrograms/g, respectively. The concentrations of the trans isomer were about 1/10 of those observed for the cis isomer. The median ratios of the Cefprozil concentration in tonsillar tissue to that in plasma were 0.37 and 0.47 for patients receiving a 7.5- or a 20-mg/kg oral dose of Cefprozil, respectively. The corresponding median ratios for the adenoidal tissue were 0.46 and 0.82, respectively. The Cefprozil concentrations in either the tonsillar or the adenoidal tissue at both dose levels over 3.17 h after dosing are much higher than the MICs for common pathogens which cause pharyngitis or tonsillitis.

  • oral absolute bioavailability and intravenous dose proportionality of Cefprozil in humans
    The Journal of Clinical Pharmacology, 1992
    Co-Authors: Wen Chyi Shyu, R. B. Wilber, K A Pittman, D A Campbell, Vinod R Shah, Rashmi H. Barbhaiya
    Abstract:

    : The absolute bioavailability (F) and dose proportionality of Cefprozil were investigated in a parallel design study with an embedded two-way crossover leg. Twenty-four healthy male subjects divided into 3 dosing groups received a single 250-, 500-, or 1000-mg dose of Cefprozil by a 30-minute intravenous infusion. Subjects assigned to the 500-mg dose group also received a 500-mg oral dose of Cefprozil in crossover manner with a wash-out period of 7 days between each treatment. Cefprozil consists of cis and trans isomers in an approximate 90:10 ratio. Serial blood and urine samples were collected and analyzed for the concentrations of the cis and trans isomers of the cephalosporin using high-pressure liquid chromatographic assay with UV detection methods. After the 250-, 500-, and 1000-mg intravenous administration of Cefprozil, the peak concentrations were 13.2, 26.0, and 48.5 micrograms/mL, and area under the plasma concentration versus time profiles were 17.2, 31.4, and 58.1 micrograms.hour/mL, respectively, for the cis isomer increasing in a dose proportional manner. Total body clearance, renal clearance, and volume of distribution at steady state, adjusted for body weight, were not significantly different among all groups. Mean residence time, elimination half-life, and urinary recovery were invariant with the dose. Based on the plasma and urine data, the estimates of F were 89% and 94% for the cis isomer, respectively. The plasma concentrations of the trans isomer were about 1/10th of the cis isomer, and all parameters were similar to those observed for the cis isomer. In summary, Cefprozil exhibits linear pharmacokinetics and is essentially completely absorbed after oral administration.

K A Pittman - One of the best experts on this subject based on the ideXlab platform.

  • oral absolute bioavailability and intravenous dose proportionality of Cefprozil in humans
    The Journal of Clinical Pharmacology, 1992
    Co-Authors: Wen Chyi Shyu, R. B. Wilber, K A Pittman, D A Campbell, Vinod R Shah, Rashmi H. Barbhaiya
    Abstract:

    : The absolute bioavailability (F) and dose proportionality of Cefprozil were investigated in a parallel design study with an embedded two-way crossover leg. Twenty-four healthy male subjects divided into 3 dosing groups received a single 250-, 500-, or 1000-mg dose of Cefprozil by a 30-minute intravenous infusion. Subjects assigned to the 500-mg dose group also received a 500-mg oral dose of Cefprozil in crossover manner with a wash-out period of 7 days between each treatment. Cefprozil consists of cis and trans isomers in an approximate 90:10 ratio. Serial blood and urine samples were collected and analyzed for the concentrations of the cis and trans isomers of the cephalosporin using high-pressure liquid chromatographic assay with UV detection methods. After the 250-, 500-, and 1000-mg intravenous administration of Cefprozil, the peak concentrations were 13.2, 26.0, and 48.5 micrograms/mL, and area under the plasma concentration versus time profiles were 17.2, 31.4, and 58.1 micrograms.hour/mL, respectively, for the cis isomer increasing in a dose proportional manner. Total body clearance, renal clearance, and volume of distribution at steady state, adjusted for body weight, were not significantly different among all groups. Mean residence time, elimination half-life, and urinary recovery were invariant with the dose. Based on the plasma and urine data, the estimates of F were 89% and 94% for the cis isomer, respectively. The plasma concentrations of the trans isomer were about 1/10th of the cis isomer, and all parameters were similar to those observed for the cis isomer. In summary, Cefprozil exhibits linear pharmacokinetics and is essentially completely absorbed after oral administration.

  • pharmacokinetic interactions of Cefprozil with food propantheline metoclopramide and probenecid in healthy volunteers
    The Journal of Clinical Pharmacology, 1992
    Co-Authors: U A Shukla, K A Pittman, Rashmi H. Barbhaiya
    Abstract:

    Cefprozil, a new oral cephalosporin antibiotic, is composed of cis and trans isomers in an approximate 90:10 ratio. The objectives of this study were: (1) to assess the effects of alterations in gastrointestinal motility by metoclopramide and propantheline on the pharmacokinetics of cis and trans isomers of Cefprozil, and to compare them with the effects of food on the pharmacokinetics of Cefprozil; (2) to assess the effects of inhibition of renal tubular secretion by probenecid on the pharmacokinetics of Cefprozil isomers. In this four-way crossover study, 15 healthy male volunteers received a 1000-mg dose of Cefprozil after fasting, pretreatment with metoclopramide or propantheline, after breakfast, or after probenecid in an incomplete, balanced block design. There was a 1-week washout period between each treatment. Blood and urine samples collected over a 24-hour period were assayed for the cis and trans isomers. The concentrations of the trans isomers were generally 1/10 of the cis isomer. The means and variances of the pharmacokinetic parameters of the cis and trans isomers of Cefprozil were similar in fasting subjects and were affected in a parallel manner by food, metoclopramide, propantheline, and probenecid. The pharmacokinetics of the cis isomer under the fasting condition were as follows: maximum peak plasma concentration (Cmax), 14.0 ± 2.7 μg/mL; median time to reach Cmax (tmax), 1.5 (range, 1.0–3.5) hours; half-life (t 1/2), 1.24 ± 0.27 hours; area under the concentration (AUC0-∞), 47.3 ± 7.7 μg · hour/mL; mean residence time after oral administration (MRTpo), 2.9 ± 0.4 hours; CLB, 219 ± 60 mL/minute; and Xu% (percent cumulative urinary excretion in 0–24 hours), 68.1 ± 12.5. Propantheline delayed the tmax and significantly increased the MRTpo of the Cefprozil isomers, relative to the fasting state, but other pharmacokinetic parameters were not significantly altered. Metoclopramide reduced the tmax and significantly decreased the MRTpo of both isomers of Cefprozil, but other pharmacokinetic parameters were not significantly altered. Food slightly delayed the tmax but did not have a significant effect on other pharmacokinetic parameters of either isomer. Pretreatment with probenecid resulted in a significant increase in the t1/2, Cmax, AUC0-∞, and MRTpo, and in a significant decrease in the CLR of each isomer, indicating that probenecid competitively inhibits renal tubular secretion of Cefprozil. In summary, the extent of absorption of Cefprozil was not affected by drugs that change gastric motility nor by concurrent administration of food. Probenecid significantly decreased the renal clearance and prolonged the t1/2 of Cefprozil, indicating that renal tubular secretion is a significant pathway in elimination of Cefprozil.

  • excretion of Cefprozil into human breast milk
    Antimicrobial Agents and Chemotherapy, 1992
    Co-Authors: Wen Chyi Shyu, R. B. Wilber, K A Pittman, D A Campbell, Vinod R Shah, J Venitz, V Jaganathan, Rashmi H. Barbhaiya
    Abstract:

    The excretion of Cefprozil into breast milk in nine healthy, lactating female subjects was investigated. Each subject received a single 1,000-mg oral dose of Cefprozil consisting of cis and trans isomers in an approximately 90:10 ratio. Serial blood, urine, and breast milk samples were collected and analyzed for the concentrations of the cis and trans isomers by a specific high-pressure liquid chromatography-UV assay. The mean pharmacokinetic parameters for both isomers were essentially the same. The mean peak concentrations in plasma for the cis isomer were 14.8 micrograms/ml, and the area under the concentration curve was 54.8 micrograms.h/ml. The mean values of elimination half-life, renal clearance, and urinary excretion for the cis isomer were 1.69 h, 164 ml/min, and 60%, respectively. The mean concentrations in milk of the cis isomer over a 24-h period ranged from 0.25 to 3.36 micrograms/ml, with the maximum concentration appearing at 6 h after dosing. The average maximum concentration in milk of the trans isomer was less than 0.26 micrograms/ml. The concentrations of the trans isomer in plasma and in breast milk were about 1/10 of those for the cis isomer. Less than 0.3% of the dose was excreted in breast milk for both isomers of Cefprozil. Even if one assumes that the concentration of Cefprozil in milk remains constant at 3.36 micrograms/ml (the highest concentration of Cefprozil observed in breast milk), an infant ingesting an average of 800 ml of milk per day will be exposed to a maximum amount of about 3 mg of Cefprozil per day. This value represents about 0.3% of the maternal dose. Low excretion of Cefprozil in breast milk and the excellent safety profile of Cefprozil suggest that this cephalosporin may be administered to nursing mothers when indicated.

  • effect of antacid on the bioavailability of Cefprozil
    Antimicrobial Agents and Chemotherapy, 1992
    Co-Authors: Wen Chyi Shyu, R. B. Wilber, K A Pittman, Rashmi H. Barbhaiya
    Abstract:

    The effect of antacid on the bioavailability of Cefprozil was investigated in a two-way crossover study. Eight healthy male subjects received a single 500-mg oral dose of Cefprozil with and without coadministration of 30 ml of an antacid suspension containing magnesium hydroxide and aluminum hydroxide (Maalox). Cefprozil consists of cis and trans isomers in an approximate 90:10 ratio. When Cefprozil was administered alone (treatment A), the mean maximum concentrations (Cmax) of the cis and trans isomers were 9.2 and 1.2 micrograms/ml, respectively. When Cefprozil was coadministered with Maalox (treatment B), the Cmax values of the cis and trans isomers were 8.7 and 1.3 micrograms/ml, respectively. The mean values of the area under the curve from time zero to infinity (AUC0-infinity) were 27.7 and 3.5 micrograms.h/ml for treatment A and 27.5 and 3.5 micrograms.h/ml for treatment B for the cis and trans isomers, respectively. The other pharmacokinetic parameters, time to Cmax, elimination half-life, mean residence time, renal clearance, and percent urinary excretion, were essentially the same for the two isomers. The respective values of the elimination half-life for the cis and trans isomers were 1.36 and 1.32 h for treatment A and 1.36 and 1.42 h for treatment B. Mean urinary excretion was 63 and 60% for treatment A and 58 and 56% for treatment B for the cis and trans isomers, respectively. No significant differences between the two treatments were found for any of the pharmacokinetic parameters for either isomer. For the cis isomer, bioavailability point estimates (90% confidence intervals) of the mean Cmax and AUG0-infinity values for the Maalox treatment relative to those for the reference treatment were 95% (87%, 103%) and 99% (95%, 104%), respectively. For the trans isomer, the value were 109% (92%, 126%) for Cmax and 97% (88%, 106%) for AUC0-infinity. On the basis of the results of this study, it is concluded that the bioavailability of Cefprozil is not affected by the coadministration of Maalox.

  • comparison of Cefprozil and cefaclor pharmacokinetics and tissue penetration
    Antimicrobial Agents and Chemotherapy, 1990
    Co-Authors: Rashmi H. Barbhaiya, R. B. Wilber, Wen Chyi Shyu, U A Shukla, Carol Gleason, K A Pittman
    Abstract:

    The pharmacokinetics and tissue penetration, as judged by skin blister fluid, of Cefprozil and cefaclor were examined in 12 healthy male volunteers. Doses of 250 and 500 mg of each drug were given to fasting subjects in a crossover fashion. Serially obtained plasma, skin blister fluid, and urine samples were analyzed for Cefprozil or cefaclor by validated high-pressure liquid chromatographic methods. After oral administration of 250 and 500 mg of Cefprozil, mean concentrations in plasma rose to peak levels (Cmax) of 6.1 and 11.2 micrograms/ml, respectively, and those of cefaclor were 10.6 and 17.3 micrograms/ml, respectively. The elimination half-life of Cefprozil (1.3 h) was significantly longer than that of cefaclor (0.6 h), and as a result, the area under the curve for Cefprozil was about two times greater than that for cefaclor. Both cephalosporins were primarily excreted unchanged in urine. The mean skin blister Cmax values were 3.0 and 5.8 micrograms/ml for Cefprozil and 3.6 and 6.5 micrograms/ml for cefaclor after the 250- and 500-mg oral doses, respectively. The mean Cmax values in skin blister fluid for both cephalosporins were comparable and were significantly lower than the corresponding Cmax values in plasma. However, the levels of Cefprozil and cefaclor in skin blister fluid declined more slowly than they did in plasma. The skin blister fluid half-life estimates for Cefprozil were significantly longer than they were for cefaclor. Parallel to the observation in plasma, the mean skin blister fluid areas under the curve for Cefprozil were significantly higher than they were for cefaclor. The plasma and skin blister fluid pharmacokinetic analyses suggest that the exposure of humans to Cefprozil is significantly greater than that to cefaclor at the same dose.

Gerson H Aronovitz - One of the best experts on this subject based on the ideXlab platform.

  • open label parallel group multicenter randomized study of Cefprozil versus erythromycin in children with group a streptococcal pharyngitis tonsillitis
    Clinical Therapeutics, 2001
    Co-Authors: Itzhak Brook, Gerson H Aronovitz, Michael E Pichichero
    Abstract:

    Abstract Background: Cefprozil and erythromycin are acceptable alternatives to penicillin in the treatment of pharyngitis/tonsillitis due to group A beta-hemolytic streptococcus (GABHS). Objective: The purpose of this trial was to determine the relative efficacy and tolerability of Cefprozil and erythromycin in the treatment of pediatric pharyngitis/tonsillitis due to GABHS. Methods: This trial compared the bacteriologic and clinical efficacy of erythromycin and Cefprozil in children 2 to 12 years of age with culture-documented GABHS pharyngitis/tonsillitis. Children who were allergic to penicillin, Cefprozil, or erythromycin were excluded. Patients were prospectively randomly assigned to receive 10 days of oral therapy with either Cefprozil suspension 15 mg/kg per day in 2 divided doses or erythromycin ethylsuccinate suspension 30 mg/kg per day in 3 divided doses. Primary efficacy end points were bacteriologic and clinical response 2 to 8 days after treatment ended. The frequency and severity of adverse events and their relationship to treatment were also assessed. Results: A total of 199 patients were enrolled and treated (Cefprozil, 99; erythromycin, 100); 12 patients in the Cefprozil group and 15 in the erythromycin group were not evaluable. The GABHS eradication rate was significantly higher with Cefprozil (95%) than with erythromycin (74%) ( P = 0.001). The posttreatment carrier rate was lower in the Cefprozil group (5%) than in the erythromycin group (18%) (95% CI, −22.3 to −3.8). Clinical cure rate was 90% (78/87) with Cefprozil and 91% (77/85) with erythromycin ( P = 0.95) (treatment group difference, −0.93; 95% CI, −9.9% to 8.0%). The overall incidence of drug-related adverse events was not significantly different in the 2 groups (11% with Cefprozil, 18% with erythromycin). The most common adverse events were diarrhea and vomiting. Two patients in the erythromycin group discontinued therapy because of adverse events. Conclusions: The bacteriologic eradication rate was significantly greater with Cefprozil compared with erythromycin in children with pharyngitis/tonsillitis. Both Cefprozil and erythromycin produced a clinical cure in > 90% of patients.

  • treatment of upper and lower respiratory tract infections clinical trials with Cefprozil
    Pediatric Infectious Disease Journal, 1998
    Co-Authors: Gerson H Aronovitz
    Abstract:

    The oral second generation cephalosporin Cefprozil has a broad spectrum microbiologic profile, with good in vitro activity against respiratory pathogens; 90% or more of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolates are susceptible to Cefprozil. Clinical trials o