Saquinavir

14,000,000 Leading Edge Experts on the ideXlab platform

Scan Science and Technology

Contact Leading Edge Experts & Companies

Scan Science and Technology

Contact Leading Edge Experts & Companies

The Experts below are selected from a list of 3399 Experts worldwide ranked by ideXlab platform

Jintanat Ananworanich - One of the best experts on this subject based on the ideXlab platform.

  • reducing the boosting dose of ritonavir does not affect Saquinavir plasma concentrations in hiv 1 infected individuals
    AIDS, 2009
    Co-Authors: Jasper Van Der Lugt, Jintanat Ananworanich, Joep M A Lange, Meena Gorowara, Anchalee Avihingsanon, David M Burger, Kancharat Sringam, Stephen J Kerr, Ferdinand W N M Wit, Kiat Ruxrungtham
    Abstract:

    Currently, the optimal boosting dose for Saquinavir is unknown. Therefore, we evaluated the pharmacokinetics profiles in a cross over setting comparing Saquinavir/ritonavir 1500/50 mg (plus NRTI backbone) to Saquinavir/ritonavir 1500/100 mg in the same HIV-infected, Thai individuals. The 50% reduction of ritonavir boosting did not result in a change in the pharmacokinetics of Saquinavir, whereas the ritonavir exposure was significantly lower when a dose of 50 mg was administered.

  • pharmacokinetics and 24 week efficacy safety of dual boosted Saquinavir lopinavir ritonavir in nucleoside pretreated children
    Pediatric Infectious Disease Journal, 2005
    Co-Authors: Jintanat Ananworanich, Kiat Ruxrungtham, Andrew F. Hill, Pope Kosalaraksa, Umaporn Siangphoe, Alina S Bergshoeff, Chitsanu Pancharoen, Chulapan Engchanil, David M Burger
    Abstract:

    OBJECTIVE: To assess the pharmacokinetics and 24-week efficacy and safety of dual boosted Saquinavir/lopinavir/ritonavir combination in children. DESIGN: Twenty reverse transcription inhibitor-pretreated children at 2 centers in Thailand were treated with Saquinavir/lopinavir/ritonavir in an open label, single arm, 6-month prospective study. The dosage was 50 mg/kg twice daily (bid) for Saquinavir and 230/57.5 mg/m bid for lopinavir/ritonavir. Ten children also received lamivudine. METHODS: Samples were collected for a 12-hour pharmacokinetic profile in all children. Plasma concentrations of Saquinavir, lopinavir and ritonavir were determined using a validated high performance liquid chromatography technique. RESULTS: At baseline, the median age was 8.5 years, with human immunodeficiency virus (HIV) RNA 4.9 log10 copies/mL, CD4 count 129 cells/microL and CD4%, 6.5%. Median area under the concentration curve at 0-12 hours and Cmin were 39.4 mg/L.h and 1.4 mg/L for Saquinavir and 118 mg/L.hr and 5.9 mg/L for lopinavir. After 24 weeks of treatment, HIV RNA was suppressed below 400 copies/mL for 16 of 20 (80%) children (intent-to-treat analysis) and below 50 copies/mL for 12 of 20 children (60%), and CD4% (count) rose by a median of 6% (216 cells/microL). Median changes of triglyceride and total cholesterol were 56 and 36.5 mg/dL, respectively (P = 0.01). Lopinavir Cmin 400 copies/mL, and lopinavir Cmax >15 mg/L correlated with rises in cholesterol (P < 0.05). CONCLUSION: Plasma drug concentrations of Saquinavir, lopinavir and ritonavir were at the higher limits of expected ranges for adult treatment at approved dosages (1000/100 mg bid for Saquinavir, 400/100 mg bid for lopinavir/ritonavir). The regimen was well-tolerated and had good efficacy at 24 weeks. This dual boosted protease inhibitor combination should be assessed in larger trials of reverse transcription inhibitor-experienced children.

  • a prospective study of efficacy and safety of once daily Saquinavir ritonavir plus two nucleoside reverse transcriptase inhibitors in treatment naive thai patients
    Antiviral Therapy, 2005
    Co-Authors: Jintanat Ananworanich, Kiat Ruxrungtham, Andrew F. Hill, Umaporn Siangphoe, Wisit Prasithsirikul, Ploenchan Chetchotisakd, Sasisopin Kiertiburanakul, Warangkana Munsakul, Phitsanu Raksakulkarn, Somboon Tansuphasawadikul
    Abstract:

    OBJECTIVE: To assess the efficacy and safety of first-line treatment with once-daily Saquinavir/ritonavir with two nucleoside reverse transcriptase inhibitors (NRTIs), as induction therapy before enrollment in a randomized trial of structured treatment interruption strategies. DESIGN: Two-hundred antiretroviral-naive patients with CD4+ cell counts between 200-350 at screening were enrolled in this open-label 24week study. METHODS: Patients were followed up every 8 weeks for CD4+ cells, HIV RNA, and clinical and laboratory toxicities. RESULTS: Two-hundred patients were enrolled with median baseline CD4+ cell count of 267 cells/microl and HIV RNA 50 118 (4.7 log10) copies/mi. After 24 weeks of treatment, 191 of 200 (96%) patients had below 400 copies/ml HIV RNA, with 177/200 (89%) below 50 copies/ml (intent to treat, missing equals failure method), with a median rise in CD4+ cell count of 122 cells/microl. There was no significant correlation between the minimum concentration of Saquinavir and HIV RNA reductions at week 8 (P = 0.957) or absolute HIV RNA at week 24 (P = 0.77). CONCLUSION: First-line highly active antiretroviral therapy (HAART) with once-daily Saquinavir/ritonavir plus two NRTIs showed strong antiviral efficacy over 24 weeks, and should be evaluated in larger prospective randomized clinical trials.

  • a prospective study of efficacy and safety of once daily Saquinavir ritonavir plus two nucleoside reverse transcriptase inhibitors in treatment naive thai patients
    Antiviral Therapy, 2005
    Co-Authors: Jintanat Ananworanich, Kiat Ruxrungtham, Umaporn Siangphoe, Andrew G Hill, Wisit Prasithsirikul, Ploenchan Chetchotisakd, Sasisopin Kiertiburanakul, Warangkana Munsakul, Phitsanu Raksakulkarn, Somboon Tansuphasawadikul
    Abstract:

    OBJECTIVE: To assess the efficacy and safety of first-line treatment with once-daily Saquinavir/ritonavir with two nucleoside reverse transcriptase inhibitors (NRTIs), as induction therapy before enrollment in a randomized trial of structured treatment interruption strategies. DESIGN: Two-hundred antiretroviral-naive patients with CD4+ cell counts between 200-350 at screening were enrolled in this open-label 24week study. METHODS: Patients were followed up every 8 weeks for CD4+ cells, HIV RNA, and clinical and laboratory toxicities. RESULTS: Two-hundred patients were enrolled with median baseline CD4+ cell count of 267 cells/microl and HIV RNA 50 118 (4.7 log10) copies/mi. After 24 weeks of treatment, 191 of 200 (96%) patients had below 400 copies/ml HIV RNA, with 177/200 (89%) below 50 copies/ml (intent to treat, missing equals failure method), with a median rise in CD4+ cell count of 122 cells/microl. There was no significant correlation between the minimum concentration of Saquinavir and HIV RNA reductions at week 8 (P = 0.957) or absolute HIV RNA at week 24 (P = 0.77). CONCLUSION: First-line highly active antiretroviral therapy (HAART) with once-daily Saquinavir/ritonavir plus two NRTIs showed strong antiviral efficacy over 24 weeks, and should be evaluated in larger prospective randomized clinical trials.

  • pharmacokinetic study of Saquinavir hard gel caps ritonavir in hiv 1 infected patients 1600 100 mg once daily compared with 2000 100 mg once daily and 1000 100 mg twice daily
    Journal of Antimicrobial Chemotherapy, 2004
    Co-Authors: Reshma Saskia Autar, Bernard Hirschel, Jintanat Ananworanich, Wichitra Apateerapong, Jongkol Sankote, Andrew Hill, David A Cooper, Joep M A Lange, P Phanuphak, K Ruxrungtham
    Abstract:

    OBJECTIVES: A pharmacokinetic comparison of three dosing regimens of Saquinavir/ritonavir was carried out: 1600/100 mg once-daily with 1000/100 mg twice-daily, and 1600/100 mg once-daily with 2000/100 mg once-daily. METHODS: Twenty patients on Saquinavir hard gel caps/ritonavir 1600/100 mg once-daily in combination with two nucleoside reverse transcriptase inhibitors for at least 4 weeks were enrolled and randomized to either Saquinavir hard gel caps/ritonavir 1000/100 mg twice-daily or 2000/100 mg once-daily. Two pharmacokinetic curves were plotted, at baseline (day 0) and 7 days after the switch. Plasma concentrations were measured at 0, 2, 4, 6, 8, 10, 12 (and 24 for once-daily dosing) hours after drug intake by validated high-performance liquid chromatographic assay (HPLC). The area under the plasma concentration-time curve (AUC0-24 or AUC0-12), maximum and minimum concentration (Cmax and Cmin) and elimination half-life were calculated using a non-compartmental model. RESULTS: Compared with Saquinavir/ritonavir 1600/100 mg once-daily dosing, the Saquinavir AUC and Cmin improved significantly when dosed as 1000/100 mg twice-daily (53% and 299%, respectively), and as 2000/100 mg once-daily (71% and 65%, respectively). Low Cmin in three subjects at baseline was corrected after switch to the other dosages. Saquinavir/ritonavir 2000/100 mg once-daily was also associated with a significant increase in Saquinavir Cmax (52%) compared with Saquinavir/ritonavir 1600/100 mg once-daily. CONCLUSIONS: Saquinavir/ritonavir when dosed as 2000/100 mg once-daily or 1000/100 mg twice-daily achieves higher Saquinavir plasma levels compared with Saquinavir/ritonavir 1600/100 mg once-daily. Taking the convenience of once-daily dosing into consideration, dosage of 2000/100 mg once-daily may be preferred.

Bernard Hirschel - One of the best experts on this subject based on the ideXlab platform.

  • pharmacokinetic study of Saquinavir hard gel caps ritonavir in hiv 1 infected patients 1600 100 mg once daily compared with 2000 100 mg once daily and 1000 100 mg twice daily
    Journal of Antimicrobial Chemotherapy, 2004
    Co-Authors: Reshma Saskia Autar, Bernard Hirschel, Jintanat Ananworanich, Wichitra Apateerapong, Jongkol Sankote, Andrew Hill, David A Cooper, Joep M A Lange, P Phanuphak, K Ruxrungtham
    Abstract:

    OBJECTIVES: A pharmacokinetic comparison of three dosing regimens of Saquinavir/ritonavir was carried out: 1600/100 mg once-daily with 1000/100 mg twice-daily, and 1600/100 mg once-daily with 2000/100 mg once-daily. METHODS: Twenty patients on Saquinavir hard gel caps/ritonavir 1600/100 mg once-daily in combination with two nucleoside reverse transcriptase inhibitors for at least 4 weeks were enrolled and randomized to either Saquinavir hard gel caps/ritonavir 1000/100 mg twice-daily or 2000/100 mg once-daily. Two pharmacokinetic curves were plotted, at baseline (day 0) and 7 days after the switch. Plasma concentrations were measured at 0, 2, 4, 6, 8, 10, 12 (and 24 for once-daily dosing) hours after drug intake by validated high-performance liquid chromatographic assay (HPLC). The area under the plasma concentration-time curve (AUC0-24 or AUC0-12), maximum and minimum concentration (Cmax and Cmin) and elimination half-life were calculated using a non-compartmental model. RESULTS: Compared with Saquinavir/ritonavir 1600/100 mg once-daily dosing, the Saquinavir AUC and Cmin improved significantly when dosed as 1000/100 mg twice-daily (53% and 299%, respectively), and as 2000/100 mg once-daily (71% and 65%, respectively). Low Cmin in three subjects at baseline was corrected after switch to the other dosages. Saquinavir/ritonavir 2000/100 mg once-daily was also associated with a significant increase in Saquinavir Cmax (52%) compared with Saquinavir/ritonavir 1600/100 mg once-daily. CONCLUSIONS: Saquinavir/ritonavir when dosed as 2000/100 mg once-daily or 1000/100 mg twice-daily achieves higher Saquinavir plasma levels compared with Saquinavir/ritonavir 1600/100 mg once-daily. Taking the convenience of once-daily dosing into consideration, dosage of 2000/100 mg once-daily may be preferred.

  • toxicity efficacy plasma drug concentrations and protease mutations in patients with advanced hiv infection treated with ritonavir plus Saquinavir
    AIDS, 1997
    Co-Authors: Patrizio Lorenzi, Sabine Yerly, Karmine Abderrakim, Marc Fathi, Luc Perrin, Jan Von Overbeck, Olivier Thierry Rutschmann, Dominique Leduc, Bernard Hirschel
    Abstract:

    OBJECTIVE: To assess the safety, efficacy and plasma drug levels of the combination of ritonavir plus Saquinavir for the treatment of advanced HIV infection. DESIGN: Multicentre pilot study. PATIENTS: Eighteen protease inhibitor-naive patients, with intolerance or contraindication to reverse transcriptase inhibitors, a median CD4 cell count of 12 x 10(6)/l (range, 1-50 x 10(6)/l), and a median HIV viraemia of 5.25 log10 copies/ml (range, 4.00-6.13 log10 copies/ml). METHODS: Patients received 600 mg twice daily of both ritonavir and Saquinavir. Viraemia was measured at baseline and at weeks 5, 9 and 13. Response was defined as a drop of viraemia of more than 1 log10 at week 5. Plasma drug levels were determined after at least 3 weeks of combined treatment: samples were collected before and 1, 2, and 4 h after the morning ingestion of both drugs. The protease gene was sequenced at baseline and under treatment. RESULTS: Among the 16 patients evaluable at week 5, 11 were responders, and among these patients, six remained responders at week 13 (two with undetectable viraemia). Study discontinuations were due to side-effects (n = 4), patient choice (n = 3), protocol violation (n = 1) and death (n = 1). Responders had higher drug levels than non-responders (P < 0.01 for Saquinavir, P = 0.04 for ritonavir). In two non-responders, development of multiple new mutations at positions 10, 20, 48, 82, 84 and 90 was observed after 5-13 weeks. CONCLUSION: The response to ritonavir plus Saquinavir in advanced HIV infection is unpredictable. A minority of patients respond with disappearance of HIV viraemia. In other patients, rapid cumulative emergence of protease mutations conferring resistance to treatment cannot always be prevented by good compliance and relatively high plasma drug levels.

  • toxicity efficacy plasma drug concentrations and protease mutations in patients with advanced hiv infection treated with ritonavir plus Saquinavir
    AIDS, 1997
    Co-Authors: Patrizio Lorenzi, Sabine Yerly, Karmine Abderrakim, Marc Fathi, Luc Perrin, Jan Von Overbeck, Olivier Thierry Rutschmann, Dominique Leduc, Bernard Hirschel
    Abstract:

    OBJECTIVE: To assess the safety, efficacy and plasma drug levels of the combination of ritonavir plus Saquinavir for the treatment of advanced HIV infection. DESIGN: Multicentre pilot study. PATIENTS: Eighteen protease inhibitor-naive patients, with intolerance or contraindication to reverse transcriptase inhibitors, a median CD4 cell count of 12 x 10(6)/l (range, 1-50 x 10(6)/l), and a median HIV viraemia of 5.25 log10 copies/ml (range, 4.00-6.13 log10 copies/ml). METHODS: Patients received 600 mg twice daily of both ritonavir and Saquinavir. Viraemia was measured at baseline and at weeks 5, 9 and 13. Response was defined as a drop of viraemia of more than 1 log10 at week 5. Plasma drug levels were determined after at least 3 weeks of combined treatment: samples were collected before and 1, 2, and 4 h after the morning ingestion of both drugs. The protease gene was sequenced at baseline and under treatment. RESULTS: Among the 16 patients evaluable at week 5, 11 were responders, and among these patients, six remained responders at week 13 (two with undetectable viraemia). Study discontinuations were due to side-effects (n = 4), patient choice (n = 3), protocol violation (n = 1) and death (n = 1). Responders had higher drug levels than non-responders (P < 0.01 for Saquinavir, P = 0.04 for ritonavir). In two non-responders, development of multiple new mutations at positions 10, 20, 48, 82, 84 and 90 was observed after 5-13 weeks. CONCLUSION: The response to ritonavir plus Saquinavir in advanced HIV infection is unpredictable. A minority of patients respond with disappearance of HIV viraemia. In other patients, rapid cumulative emergence of protease mutations conferring resistance to treatment cannot always be prevented by good compliance and relatively high plasma drug levels.

Kiat Ruxrungtham - One of the best experts on this subject based on the ideXlab platform.

  • reducing the boosting dose of ritonavir does not affect Saquinavir plasma concentrations in hiv 1 infected individuals
    AIDS, 2009
    Co-Authors: Jasper Van Der Lugt, Jintanat Ananworanich, Joep M A Lange, Meena Gorowara, Anchalee Avihingsanon, David M Burger, Kancharat Sringam, Stephen J Kerr, Ferdinand W N M Wit, Kiat Ruxrungtham
    Abstract:

    Currently, the optimal boosting dose for Saquinavir is unknown. Therefore, we evaluated the pharmacokinetics profiles in a cross over setting comparing Saquinavir/ritonavir 1500/50 mg (plus NRTI backbone) to Saquinavir/ritonavir 1500/100 mg in the same HIV-infected, Thai individuals. The 50% reduction of ritonavir boosting did not result in a change in the pharmacokinetics of Saquinavir, whereas the ritonavir exposure was significantly lower when a dose of 50 mg was administered.

  • pharmacokinetics and 24 week efficacy safety of dual boosted Saquinavir lopinavir ritonavir in nucleoside pretreated children
    Pediatric Infectious Disease Journal, 2005
    Co-Authors: Jintanat Ananworanich, Kiat Ruxrungtham, Andrew F. Hill, Pope Kosalaraksa, Umaporn Siangphoe, Alina S Bergshoeff, Chitsanu Pancharoen, Chulapan Engchanil, David M Burger
    Abstract:

    OBJECTIVE: To assess the pharmacokinetics and 24-week efficacy and safety of dual boosted Saquinavir/lopinavir/ritonavir combination in children. DESIGN: Twenty reverse transcription inhibitor-pretreated children at 2 centers in Thailand were treated with Saquinavir/lopinavir/ritonavir in an open label, single arm, 6-month prospective study. The dosage was 50 mg/kg twice daily (bid) for Saquinavir and 230/57.5 mg/m bid for lopinavir/ritonavir. Ten children also received lamivudine. METHODS: Samples were collected for a 12-hour pharmacokinetic profile in all children. Plasma concentrations of Saquinavir, lopinavir and ritonavir were determined using a validated high performance liquid chromatography technique. RESULTS: At baseline, the median age was 8.5 years, with human immunodeficiency virus (HIV) RNA 4.9 log10 copies/mL, CD4 count 129 cells/microL and CD4%, 6.5%. Median area under the concentration curve at 0-12 hours and Cmin were 39.4 mg/L.h and 1.4 mg/L for Saquinavir and 118 mg/L.hr and 5.9 mg/L for lopinavir. After 24 weeks of treatment, HIV RNA was suppressed below 400 copies/mL for 16 of 20 (80%) children (intent-to-treat analysis) and below 50 copies/mL for 12 of 20 children (60%), and CD4% (count) rose by a median of 6% (216 cells/microL). Median changes of triglyceride and total cholesterol were 56 and 36.5 mg/dL, respectively (P = 0.01). Lopinavir Cmin 400 copies/mL, and lopinavir Cmax >15 mg/L correlated with rises in cholesterol (P < 0.05). CONCLUSION: Plasma drug concentrations of Saquinavir, lopinavir and ritonavir were at the higher limits of expected ranges for adult treatment at approved dosages (1000/100 mg bid for Saquinavir, 400/100 mg bid for lopinavir/ritonavir). The regimen was well-tolerated and had good efficacy at 24 weeks. This dual boosted protease inhibitor combination should be assessed in larger trials of reverse transcription inhibitor-experienced children.

  • a prospective study of efficacy and safety of once daily Saquinavir ritonavir plus two nucleoside reverse transcriptase inhibitors in treatment naive thai patients
    Antiviral Therapy, 2005
    Co-Authors: Jintanat Ananworanich, Kiat Ruxrungtham, Andrew F. Hill, Umaporn Siangphoe, Wisit Prasithsirikul, Ploenchan Chetchotisakd, Sasisopin Kiertiburanakul, Warangkana Munsakul, Phitsanu Raksakulkarn, Somboon Tansuphasawadikul
    Abstract:

    OBJECTIVE: To assess the efficacy and safety of first-line treatment with once-daily Saquinavir/ritonavir with two nucleoside reverse transcriptase inhibitors (NRTIs), as induction therapy before enrollment in a randomized trial of structured treatment interruption strategies. DESIGN: Two-hundred antiretroviral-naive patients with CD4+ cell counts between 200-350 at screening were enrolled in this open-label 24week study. METHODS: Patients were followed up every 8 weeks for CD4+ cells, HIV RNA, and clinical and laboratory toxicities. RESULTS: Two-hundred patients were enrolled with median baseline CD4+ cell count of 267 cells/microl and HIV RNA 50 118 (4.7 log10) copies/mi. After 24 weeks of treatment, 191 of 200 (96%) patients had below 400 copies/ml HIV RNA, with 177/200 (89%) below 50 copies/ml (intent to treat, missing equals failure method), with a median rise in CD4+ cell count of 122 cells/microl. There was no significant correlation between the minimum concentration of Saquinavir and HIV RNA reductions at week 8 (P = 0.957) or absolute HIV RNA at week 24 (P = 0.77). CONCLUSION: First-line highly active antiretroviral therapy (HAART) with once-daily Saquinavir/ritonavir plus two NRTIs showed strong antiviral efficacy over 24 weeks, and should be evaluated in larger prospective randomized clinical trials.

  • a prospective study of efficacy and safety of once daily Saquinavir ritonavir plus two nucleoside reverse transcriptase inhibitors in treatment naive thai patients
    Antiviral Therapy, 2005
    Co-Authors: Jintanat Ananworanich, Kiat Ruxrungtham, Umaporn Siangphoe, Andrew G Hill, Wisit Prasithsirikul, Ploenchan Chetchotisakd, Sasisopin Kiertiburanakul, Warangkana Munsakul, Phitsanu Raksakulkarn, Somboon Tansuphasawadikul
    Abstract:

    OBJECTIVE: To assess the efficacy and safety of first-line treatment with once-daily Saquinavir/ritonavir with two nucleoside reverse transcriptase inhibitors (NRTIs), as induction therapy before enrollment in a randomized trial of structured treatment interruption strategies. DESIGN: Two-hundred antiretroviral-naive patients with CD4+ cell counts between 200-350 at screening were enrolled in this open-label 24week study. METHODS: Patients were followed up every 8 weeks for CD4+ cells, HIV RNA, and clinical and laboratory toxicities. RESULTS: Two-hundred patients were enrolled with median baseline CD4+ cell count of 267 cells/microl and HIV RNA 50 118 (4.7 log10) copies/mi. After 24 weeks of treatment, 191 of 200 (96%) patients had below 400 copies/ml HIV RNA, with 177/200 (89%) below 50 copies/ml (intent to treat, missing equals failure method), with a median rise in CD4+ cell count of 122 cells/microl. There was no significant correlation between the minimum concentration of Saquinavir and HIV RNA reductions at week 8 (P = 0.957) or absolute HIV RNA at week 24 (P = 0.77). CONCLUSION: First-line highly active antiretroviral therapy (HAART) with once-daily Saquinavir/ritonavir plus two NRTIs showed strong antiviral efficacy over 24 weeks, and should be evaluated in larger prospective randomized clinical trials.

  • lack of interaction between enfuvirtide and ritonavir or ritonavir boosted Saquinavir in hiv 1 infected patients
    The Journal of Clinical Pharmacology, 2004
    Co-Authors: Kiat Ruxrungtham, Tosca Kinchelow, Mark A. Boyd, Xiaoping Zhang, Albert Dorr, Stanley J. Kolis, Neil Buss, Eralp S Bellibas, Indravadan H. Patel
    Abstract:

    Enfuvirtide (Fuzeon) is an HIV fusion inhibitor, the first drug in a new class of antiretrovirals. The HIV protease inhibitors ritonavir and Saquinavir both inhibit cytochrome P450 (CYP450) isoenzymes, and low-dose ritonavir is often used to boost pharmacokinetic exposure to full-dose protease inhibitors. These two studies were designed to assess whether ritonavir and ritonavir-boosted Saquinavir influence the steady-state pharmacokinetics of enfuvirtide. Both studies were single-center, open-label, one-sequence crossover clinical pharmacology studies in 12 HIV-1-infected patients each. Patients received enfuvirtide (90 mg twice daily [bid], subcutaneous injection) for 7 days and either ritonavir (200 mg bid, ritonavir study, orally) or Saquinavir/ritonavir (1000/100 mg bid, Saquinavir/ritonavir study, orally) for 4 days on days 4 to 7. Serial blood samples were collected up to 24 hours after the morning dose of enfuvirtide on days 3 and 7. Plasma concentrations for enfuvirtide, enfuvirtide metabolite, Saquinavir, and ritonavir were measured using validated liquid chromatography tandem mass spectrometry methods. Efficacy and safety were also monitored. Bioequivalence criteria require the 90% confidence interval (CI) for the least squares means (LSM) of C(max) and AUC(12h) to be between 80% and 125%. In the present studies, analysis of variance showed that when coadministered with ritonavir, the ratio of LSM for enfuvirtide was 124% for C(max) (90% confidence interval [CI]: 109%-141%), 122% for AUC(12h) (90% CI: 108%-137%), and 114% for C(trough) (90% CI: 102%-128%). Although the bioequivalence criteria were not met, the increase in enfuvirtide exposure was small (< 25%) and not clinically relevant. When administered with ritonavir-boosted Saquinavir, the ratio of LSM for enfuvirtide was 107% for C(max) (90% CI: 94.3%-121%) and 114% for AUC(12h) (90% CI: 105%-124%), which therefore met bioequivalence criteria, and 126% for C(trough) (90% CI: 117%-135%). The pharmacokinetics of enfuvirtide are affected to a small extent when coadministered with ritonavir at a dose of 200 mg bid but not when coadministered with a Saquinavir-ritonavir combination (1000/100 mg bid). However, previous clinical studies have shown that such increases in enfuvirtide exposure are not clinically relevant. Thus, no dosage adjustments are warranted when enfuvirtide is coadministered with low-dose ritonavir or Saquinavir boosted with a low dose of ritonavir.

Thomas C Merigan - One of the best experts on this subject based on the ideXlab platform.

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

  • pharmacokinetic study of Saquinavir hard gel caps ritonavir in hiv 1 infected patients 1600 100 mg once daily compared with 2000 100 mg once daily and 1000 100 mg twice daily
    Journal of Antimicrobial Chemotherapy, 2004
    Co-Authors: Reshma Saskia Autar, Bernard Hirschel, Jintanat Ananworanich, Wichitra Apateerapong, Jongkol Sankote, Andrew Hill, David A Cooper, Joep M A Lange, P Phanuphak, K Ruxrungtham
    Abstract:

    OBJECTIVES: A pharmacokinetic comparison of three dosing regimens of Saquinavir/ritonavir was carried out: 1600/100 mg once-daily with 1000/100 mg twice-daily, and 1600/100 mg once-daily with 2000/100 mg once-daily. METHODS: Twenty patients on Saquinavir hard gel caps/ritonavir 1600/100 mg once-daily in combination with two nucleoside reverse transcriptase inhibitors for at least 4 weeks were enrolled and randomized to either Saquinavir hard gel caps/ritonavir 1000/100 mg twice-daily or 2000/100 mg once-daily. Two pharmacokinetic curves were plotted, at baseline (day 0) and 7 days after the switch. Plasma concentrations were measured at 0, 2, 4, 6, 8, 10, 12 (and 24 for once-daily dosing) hours after drug intake by validated high-performance liquid chromatographic assay (HPLC). The area under the plasma concentration-time curve (AUC0-24 or AUC0-12), maximum and minimum concentration (Cmax and Cmin) and elimination half-life were calculated using a non-compartmental model. RESULTS: Compared with Saquinavir/ritonavir 1600/100 mg once-daily dosing, the Saquinavir AUC and Cmin improved significantly when dosed as 1000/100 mg twice-daily (53% and 299%, respectively), and as 2000/100 mg once-daily (71% and 65%, respectively). Low Cmin in three subjects at baseline was corrected after switch to the other dosages. Saquinavir/ritonavir 2000/100 mg once-daily was also associated with a significant increase in Saquinavir Cmax (52%) compared with Saquinavir/ritonavir 1600/100 mg once-daily. CONCLUSIONS: Saquinavir/ritonavir when dosed as 2000/100 mg once-daily or 1000/100 mg twice-daily achieves higher Saquinavir plasma levels compared with Saquinavir/ritonavir 1600/100 mg once-daily. Taking the convenience of once-daily dosing into consideration, dosage of 2000/100 mg once-daily may be preferred.

Related terms

Saquinavir - 15 days free trial to Access Experts & Abstracts