Amprenavir - Explore the Science & Experts | ideXlab

Scan Science and Technology

Contact Leading Edge Experts & Companies

Amprenavir

The Experts below are selected from a list of 2643 Experts worldwide ranked by ideXlab platform

Amprenavir – Free Register to Access Experts & Abstracts

Joseph J. Eron – One of the best experts on this subject based on the ideXlab platform.

  • a 42 week open label study to assess the pharmacokinetics antiretroviral activity and safety of Amprenavir or Amprenavir plus ritonavir in combination with abacavir and lamivudine for treatment of hiv infected patients
    Clinical Infectious Diseases, 2004
    Co-Authors: Robin Wood, Mary Beth Wire, Keikawus Arastéh, Eugenio Teofilo, Joseph J. Eron, Judith Millard, Christian Trepo, Jean Michel Livrozet, Odin J. Naderer

    Abstract:

    The pharmacokinetics, antiviral activity, and safety of an Amprenavir-ritonavir (APV-RTV) 600/100 mg b.i.d. regimen and an APV-RTV 1200/200 mg q.d. regimen were studied in a human immunodeficiency virus (HIV)-infected population. The geometric least-square mean ratio (90% confidence interval) of steady-state trough concentrations, compared with that of the Amprenavir 1200 mg b.i.d. regimen, was 6.08 (4.94-7.49) for the twice-daily APV-RTV regimen, and it was 4.19 (2.90-6.08) for the daily APV-RTV regimen. The regimens were well tolerated, which supports APV-RTV as an option for twice-daily or daily therapy for HIV.

  • The Pharmacokinetics, Safety, and Initial Virologic Response of a Triple–protease Inhibitor Salvage Regimen Containing Amprenavir, Saquinavir, and Ritonavir
    Journal of acquired immune deficiency syndromes (1999), 2004
    Co-Authors: Amanda H. Corbett, Joseph J. Eron, Susan A. Fiscus, Naser L. Rezk, Angela D. M. Kashuba

    Abstract:

    The aim of this study was to quantify the change in saquinavir and Amprenavir exposure when combined and used with low-dose ritonavir; to evaluate 24-week safety and immunologic and virologic response. It was a randomized, nonblinded, prospective study. There were 11 HIV-1-infected, antiretroviral-experienced, male and female subjects > or = 18 years old, median HIV-1 RNA and CD4(+) T-cell count of 4.86 log copies/mL and 10(6) cells/mm(3), respectively. Subjects were randomly assigned to receive saquinavir 1000 mg/ritonavir 100 mg every 12 hours or Amprenavir 600 mg/ritonavir 100 mg every 12 hours for 7 days. After 12-hour pharmacokinetic sampling, the third protease inhibitor (PI) was added, and pharmacokinetics sampling was repeated 14 days later. Subsequent PI dosage adjustments were based on real-time pharmacokinetic assessment. Saquinavir did not affect Amprenavir or ritonavir pharmacokinetics. Amprenavir decreased area under the concentration-time curve (AUC(0-12h)) and C(12h) for saquinavir 82 and 61%, and 74 and 75% for ritonavir. An adjusted PI regimen of Amprenavir 600 mg/saquinavir 1400 mg/ritonavir 200 mg every 12 hours returned saquinavir exposure to baseline. At 24 weeks, HIV RNA declined a median of 1.55 log copies/mL and CD4(+) T-cell counts increased a median of 52 cells/mm(3). Gastrointestinal events predominated and were mild to moderate. These data suggest that Amprenavir/saquinavir/ritonavir may be a viable salvage regimen in heavily PI-experienced individuals. New formulations of Amprenavir and saquinavir may simplify this regimen.

  • the pharmacokinetics safety and initial virologic response of a triple protease inhibitor salvage regimen containing Amprenavir saquinavir and ritonavir
    Journal of Acquired Immune Deficiency Syndromes, 2004
    Co-Authors: Amanda H. Corbett, Joseph J. Eron, Susan A. Fiscus, Naser L. Rezk, Angela D. M. Kashuba

    Abstract:

    The aim of this study was to quantify the change in saquinavir and Amprenavir exposure when combined and used with low-dose ritonavir; to evaluate 24-week safety and immunologic and virologic response. It was a randomized, nonblinded, prospective study. There were 11 HIV-1-infected, antiretroviral-experienced, male and female subjects > or = 18 years old, median HIV-1 RNA and CD4(+) T-cell count of 4.86 log copies/mL and 10(6) cells/mm(3), respectively. Subjects were randomly assigned to receive saquinavir 1000 mg/ritonavir 100 mg every 12 hours or Amprenavir 600 mg/ritonavir 100 mg every 12 hours for 7 days. After 12-hour pharmacokinetic sampling, the third protease inhibitor (PI) was added, and pharmacokinetics sampling was repeated 14 days later. Subsequent PI dosage adjustments were based on real-time pharmacokinetic assessment. Saquinavir did not affect Amprenavir or ritonavir pharmacokinetics. Amprenavir decreased area under the concentration-time curve (AUC(0-12h)) and C(12h) for saquinavir 82 and 61%, and 74 and 75% for ritonavir. An adjusted PI regimen of Amprenavir 600 mg/saquinavir 1400 mg/ritonavir 200 mg every 12 hours returned saquinavir exposure to baseline. At 24 weeks, HIV RNA declined a median of 1.55 log copies/mL and CD4(+) T-cell counts increased a median of 52 cells/mm(3). Gastrointestinal events predominated and were mild to moderate. These data suggest that Amprenavir/saquinavir/ritonavir may be a viable salvage regimen in heavily PI-experienced individuals. New formulations of Amprenavir and saquinavir may simplify this regimen.

Brian M. Sadler – One of the best experts on this subject based on the ideXlab platform.

  • Pharmacokinetic Modeling and Simulations of Interaction of Amprenavir and Ritonavir
    Antimicrobial agents and chemotherapy, 2002
    Co-Authors: Mark Sale, Brian M. Sadler, Daniel S. Stein

    Abstract:

    Data from three pharmacokinetic drug interaction studies of Amprenavir and ritonavir were used to develop a pharmacokinetic interaction model using NONMEM (nonlinear mixed-effect model). A two-compartment linear model with first-order absorption best fit the Amprenavir data, while a one-compartment model was used to describe the ritonavir data. The inhibition of elimination of Amprenavir by ritonavir was modeled with a maximum effect (Emax) inhibition model and the observed ritonavir concentration. Monte Carlo simulation was then used to predict Amprenavir concentrations for various combinations of Amprenavir and ritonavir in twice-daily and once-daily dosing regimens. Simulated minimum Amprenavir concentrations in plasma (Cmin) in twice-daily and once-daily dosing regimens were compared with protein binding-adjusted 50% inhibitory concentrations (IC50s) for clinical human immunodeficiency virus isolates with different susceptibilities to protease inhibitors (central tendency ratios). The model based on the first two studies predicted the results of the third study. Data from all three studies were then combined to refine the final model. The observed and simulated noncompartmental pharmacokinetic parameters agreed well. From this model, several candidate drug regimens were simulated. These simulations suggest that, in patients who have clinically failed a traditional Amprenavir regimen, a regimen of 600 mg of Amprenavir with 100 mg of ritonavir twice daily would result in Cmin-to-IC50 ratios similar to that of 1,200 mg of Amprenavir twice daily alone for wild-type viruses. In addition, once-daily regimens that result in C(min)s above the protein binding-corrected IC50s for wild-type virus are clearly feasible.

  • Pharmacokinetic Study of Human Immunodeficiency Virus Protease Inhibitors Used in Combination with Amprenavir
    Antimicrobial agents and chemotherapy, 2001
    Co-Authors: Brian M. Sadler, Catherine Gillotin, Joseph J. Eron, Yu Lou, Richard Haubrich, William Lang, Daniel S. Stein

    Abstract:

    In an open-label, randomized, multicenter, multiple-dose pharmacokinetic study, we determined the steady-state pharmacokinetics of Amprenavir with and without coadministration of indinavir, nelfinavir, or saquinavir soft gel formulation in 31 human immunodeficiency virus type 1-infected subjects. The results indicated that Amprenavir plasma concentrations were decreased by saquinavir soft gel capsule (by 32% for area under the concentration-time curve at steady state [AUC ss ] and 37% for peak plasma concentration at steady state [ C max,ss ]) and increased by indinavir (33% for AUC ss ). Nelfinavir significantly increased Amprenavir minimum drug concentration at steady state (by 189%) but did not affect Amprenavir AUC ss or C max,ss . Nelfinavir and saquinavir steady-state pharmacokinetics were unchanged by coadministration with Amprenavir compared with the historical monotherapy data. Concentrations of indinavir, coadministered with Amprenavir, in plasma decreased in both single-dose and steady-state evaluations. The changes in Amprenavir steady-state pharmacokinetic parameters, relative to those for Amprenavir alone, were not consistent among protease inhibitors, nor were the changes consistent with potential interactions in CYP3A4 metabolism or P-glycoprotein transport. No dose adjustment of either protease inhibitor in any of the combinations studied is needed.

  • In Vivo Effect of α1-Acid Glycoprotein on Pharmacokinetics of Amprenavir, a Human Immunodeficiency Virus Protease Inhibitor
    Antimicrobial agents and chemotherapy, 2001
    Co-Authors: Brian M. Sadler, Catherine Gillotin, Yu Lou, Daniel S. Stein

    Abstract:

    Observations from early clinical pharmacology studies of Amprenavir, an inhibitor of human immunodeficiency virus type 1 (HIV-1) protease that is highly bound to human plasma proteins (∼90%), showed the single-dose pharmacokinetics of Amprenavir to be variable between and within individuals. A cross-study analysis of various demographic, laboratory, and clinical covariates was therefore performed. Differences in Amprenavir pharmacokinetics could be due to variable concentrations in α 1 -acid glycoprotein (AAG), the predominant plasma protein to which Amprenavir binds. Therefore, AAG was considered an important factor to study since the literature suggested that AAG levels vary by race, age, and weight and following trauma or infection, including HIV disease. Pooled data from three single-dose studies analyzed by stepwise linear regression indicated that AAG concentrations significantly correlated with age and race and that only AAG concentrations were a significant predictor of Amprenavir apparent total clearance (CL/F). A significant inverse linear relationship was found between AAG and Amprenavir CL/F. Compared to white subjects, black subjects had significantly lower AAG concentrations and therefore significantly higher Amprenavir CL/F. Although AAG has a significant influence on the variability of total drug pharmacokinetics, unbound, or free, drug concentrations are not affected by AAG concentrations. Incorrect conclusions could be drawn on the pharmacokinetics of highly protein-bound drugs if AAG concentration is not included in the analysis.

Yu Lou – One of the best experts on this subject based on the ideXlab platform.

  • Ritonavir Increases Plasma Amprenavir (APV) Exposure to a Similar Extent when Coadministered with either FosAmprenavir or APV
    Antimicrobial agents and chemotherapy, 2006
    Co-Authors: Mary Beth Wire, Mark J. Shelton, Yu Lou, Katherine L. Baker, Lori S. Jones, Greg J. Thomas, M.m. Berrey

    Abstract:

    To compare the effect of ritonavir on plasma Amprenavir pharmacokinetics, healthy adults received either fosAmprenavir (700 mg twice a day [BID]) or Amprenavir (600 mg BID) alone and in combination with ritonavir (100 mg BID). Ritonavir increased plasma Amprenavir pharmacokinetic parameters to a similar extent when coadministered with either fosAmprenavir or Amprenavir.

  • Single-Dose Safety and Pharmacokinetics of Amprenavir (141W94), a Human Immunodeficiency Virus Type 1 (HIV-1) Protease Inhibitor, in HIV-Infected Children
    Antimicrobial agents and chemotherapy, 2005
    Co-Authors: Ram Yogev, Yu Lou, Andrea Kovacs, Ellen G. Chadwick, James Homans, William T. Symonds

    Abstract:

    A phase I, open-label, dose-escalating trial was conducted to evaluate the safety, tolerability, and pharmacokinetics of single, oral doses of Amprenavir (141W94), a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) protease, in 20 HIV-infected children 4 to 12 years of age. The doses of Amprenavir evaluated, 5, 10, 15, and 20 mg/kg of body weight, were comparable to those evaluated in adult phase I and II studies. The most common clinical adverse event associated with Amprenavir, administered as soft gelatin capsules, was nausea. Amprenavir was rapidly absorbed, with a mean time to maximum concentration ( T max ) occurring 0.95 to 1.58 h after dosing. The area under the concentration-time curve (AUC 0 → ∞ ) was dose proportional, and the mean maximum plasma concentration ( C max ) increased linearly in a less than dose-proportional manner. Amprenavir was eliminated relatively slowly, with a mean terminal-phase half-life ( t 1/2 ) of 6.17 to 8.28 h. The t 1/2 , apparent total clearance, and apparent volume of distribution during the elimination phase were dose independent. Considerable interpatient variability was seen for all pharmacokinetic parameters of Amprenavir. The results of this study suggest that 20 mg of Amprenavir/kg administered twice a day should be used in future pediatric studies.

  • pharmacokinetics and pharmacodynamics of methadone enantiomers after coadministration with Amprenavir in opioid dependent subjects
    Pharmacotherapy, 2004
    Co-Authors: Craig W. Hendrix, Mary Beth Wire, Yu Lou, John Wakeford, George E. Bigelow, Elizabeth A. Martinez, Jared Christopher, Edward J. Fuchs, J. Snidow

    Abstract:

    Study Objective. To investigate the steady-state pharmacokinetics of methadone enantiomers when coadministered with Amprenavir.

    Design. Prospective, open-label, within-subject pharmacokinetic study.

    Setting. University research center.

    Subjects. Nineteen opioid-dependent, methadone-maintained, healthy individuals were enrolled.

    Intervention. On study day 1, subjects received their usual once-daily dose of methadone alone. On study days 2–11, they received the same once-daily methadone dose plus Amprenavir 1200 mg twice/day Serial blood samples were collected over 24 hours on study days 1 and 11 for measurement of plasma R- and S-methadone, and over 12 hours on day 11 for serum Amprenavir concentrations.

    Measurements and Main Results. Standard pharmacokinetic parameters were determined from the concentrations and compared between the two treatments (methadone alone vs methadone with Amprenavir). Subjects served as their own control for methadone comparisons, and Amprenavir comparisons were made by using a historic control group (38 healthy men). Opioid-effect measures were assessed throughout the study. Coadministration of Amprenavir with methadone resulted in a 3–4-hour delay in plasma R- and S-methadone enantiomer peak concentrations at steady state (Cmax-ss). The active R-methadone enantiomer area under the plasma concentration–time curve during a dosing interval (AUCτ-ss), Cmax-ss, and the minimum plasma concentration at steady state (Cmin-ss) were decreased by 13%, 25%, and 21%, respectively, after coadministration of methadone and Amprenavir. The inactive S-enantiomer AUCτ-ss, Cmax-ss, and Cmin-ss were decreased by 40%, 48%, and 52%, respectively. No clinically significant changes were noted in opioid pharmacodynamic effects, and there was no evidence of opioid withdrawal. No methadone dosage was changed in any subject.

    Conclusion. No a priori adjustment in methadone dosage is required during coadministration with Amprenavir as there is only a small effect on R-methadone exposure and no evidence of opioid withdrawal.