Institute Of Recerca Of Lhospital Of La Santa Creu I Sant Pau Iib Sant Pau

Sant Martí, Spain

Institute Of Recerca Of Lhospital Of La Santa Creu I Sant Pau Iib Sant Pau

Sant Martí, Spain

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Estevez J.A.,Institute Of Recerca Of Lhospital Of La Santa Creu I Sant Pau Iib Sant Pau | Estevez J.A.,Autonomous University of Barcelona | Molto J.,Hospital Universitari Germans Trias i Pujol | Molto J.,Autonomous University of Barcelona | And 13 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2012

Objectives: To evaluate the pharmacokinetics, tolerability and safety of 300 mg of atazanavir boosted with 100 or 50 mg of ritonavir, both once daily, at steady state. Methods: This was a single-blind, multiple-dose, crossover, sequence-randomized trial. Thirteen healthy HIV-1-negative men received witnessed once-daily doses of atazanavir (300 mg) and 100 or 50 mg of ritonavir for 10 days (15 day washout). Atazanavir and ritonavir plasma concentrations were determined for 24 h on day 10. Log-transformed individual pharmacokinetic parameters were compared between treatments (analysis of variance); the difference between treatments on the log scale and 95% CIs were calculated. Fasting cholesterol, triglycerides, glucose and bilirubin plasma levels were measured at the beginning and end of each period and compared (Wilcoxon signed rank test). Gastrointestinal symptoms and other events were recorded. Results: Ritonavir C max and the AUC 0-24 were lower after the 50 mg booster dose than after 100 mg [geometric mean ratio (GMR) (95% CI), 0.40 (0.31-0.51) and 0.35 (0.29-0.42), respectively]. No differences were observed in atazanavir exposure with 50 or 100 mg of ritonavir [GMR C max (95% CI), 1.00 (0.79-1.28); GMR AUC 0-24 (95% CI), 0.98 (0.79-1.21)]. Atazanavir trough concentration was >0.15 mg/L in all volunteers. Total and low-density lipoprotein cholesterol increased 0.40 mM (P = 0.01) and 0.37 mM (P = 0.003) from their corresponding baseline value during the 100 mg dosing period; there were no significant changes on 50 mg. Mild increases in bilirubin were detected on day 10 after both treatments without differences between treatments. Conclusions: In spite of higher exposure to ritonavir with 100 mg, atazanavir exposure was equivalent; the lipid profile was better under the lower booster dose (50 mg). © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


PubMed | Institute Of Recerca Of Lhospital Of La Santa Creu I Sant Pau Iib Sant Pau
Type: Journal Article | Journal: The Journal of antimicrobial chemotherapy | Year: 2012

To evaluate the pharmacokinetics, tolerability and safety of 300 mg of atazanavir boosted with 100 or 50 mg of ritonavir, both once daily, at steady state.This was a single-blind, multiple-dose, crossover, sequence-randomized trial. Thirteen healthy HIV-1-negative men received witnessed once-daily doses of atazanavir (300 mg) and 100 or 50 mg of ritonavir for 10 days (15 day washout). Atazanavir and ritonavir plasma concentrations were determined for 24 h on day 10. Log-transformed individual pharmacokinetic parameters were compared between treatments (analysis of variance); the difference between treatments on the log scale and 95% CIs were calculated. Fasting cholesterol, triglycerides, glucose and bilirubin plasma levels were measured at the beginning and end of each period and compared (Wilcoxon signed rank test). Gastrointestinal symptoms and other events were recorded.Ritonavir C(max) and the AUC were lower after the 50 mg booster dose than after 100 mg [geometric mean ratio (GMR) (95% CI), 0.40 (0.31-0.51) and 0.35 (0.29-0.42), respectively]. No differences were observed in atazanavir exposure with 50 or 100 mg of ritonavir [GMR C(max) (95% CI), 1.00 (0.79-1.28); GMR AUC (95% CI), 0.98 (0.79-1.21)]. Atazanavir trough concentration was >0.15 mg/L in all volunteers. Total and low-density lipoprotein cholesterol increased 0.40 mM (P=0.01) and 0.37 mM (P=0.003) from their corresponding baseline value during the 100 mg dosing period; there were no significant changes on 50 mg. Mild increases in bilirubin were detected on day 10 after both treatments without differences between treatments.In spite of higher exposure to ritonavir with 100 mg, atazanavir exposure was equivalent; the lipid profile was better under the lower booster dose (50 mg).


PubMed | Hospital Universitari Germans Trias i Pujol and Institute Of Recerca Of Lhospital Of La Santa Creu I Sant Pau Iib Sant Pau
Type: Journal Article | Journal: British journal of clinical pharmacology | Year: 2016

The aim of the present study was to develop a simultaneous population pharmacokinetic model for atazanavir (ATV) incorporating the effect of ritonavir (RTV) on clearance to predict ATV concentrations under different dosing regimens in HIV-1-infected patients.A Cross-sectional study was carried out in 83 HIV-1-infected adults taking ATV 400mg or ATV 300mg/RTV 100mg once daily. Demographic and clinical characteristics were registered and blood samples collected to measure drug concentrations. A population pharmacokinetic model was constructed using nonlinear mixed-effects modelling and used to simulate six dosing scenarios.The selected one-compartmental model described the pharmacokinetics of RTV and ATV simultaneously, showing exponential, direct inhibition of ATV clearance according to the RTV plasma concentration, which explained 17.5% of the variability. A mean RTV plasma concentration of 0.63mg lA one-compartment simultaneous model can describe the pharmacokinetics of RTV and ATV, including the effect of RTV plasma concentrations on ATV clearance. This model is promising for predicting individuals ATV concentrations in clinical scenarios, and supports further clinical trials of once-daily doses of ATV 300mg/RTV 50mg or ATV 200mg/RTV 100mg to confirm efficacy and safety.

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