The pharmacokinetics, safety and efficacy of boosted saquinavir tablets in HIV type-1-infected Pregnant women

Abstract

Background: Pregnancy affects the pharmacokinetics of most protease inhibitors. Saquinavir, when administered in a tablet formulation, has not been studied extensively in this setting. Methods: A pharmacokinetic, prospective, multicentre trial of HIV type-l-infected pregnant women treated with saquinavir (500 mg tablets) boosted with ritonavir at a dose of 1,000/100 mg twice daily plus a nucleoside backbone was conducted. Pharmacokinetic curves were recorded for 12 h in the second trimester (week 20), the third trimester (week 33 ±2) and post-parturn (weeks 4-6). B1ood was sampled pre-dosing and at 1, 2, 3, 4 6, 8, 10 and 12 h post-dosing. Pharmacokinetic parameters were calculated using WinNonlin software version 4.1. Results: A total of 37 women were included in the analysis. Mean (±SD) values for saquinavir area under the curve (AUC0-12h) were 23.47 h·mg/l (11.92) at week 20 (n=16), 23.65 h·mg/l (9.07) at week 33 (n=31) and 25.00 h·mg/l (11.81) post-partum (n=9). There was no significant difference in the saquinavir AUC0-12h when comparing the data during pregnancy and post-partum. Subtherapeutic plasma concentrations of saquinavir (defined as <0.10 mg/l) were not observed throughout the study. No major safety concerns were noted. Conclusions: Saquinavir exposure in the new tablet formulation generates adequate saquinavite concentrations throughout the course of pregnancy and is safe to use; therefore, no dose adjustment during pregnancy is needed. © 2009 International Medical Press.