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

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-1-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 +/- 2), the third trimester (week 33 +/- 2) and post-partum (weeks 4-6). Blood 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 (AUC(0-12h)) were 23.47 h center dot mg/l (11.92) at week 20 (n=16), 23.65 h center dot mg/l (9.07) at week 33 (n=31) and 25.00 h center dot mg/l (11.81) post-partum (n=9). There was no significant difference in the saquinavir AUC(0-12h) 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 saquinavir concentrations throughout the course of pregnancy and is safe to use; therefore, no dose adjustment during pregnancy is needed