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-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•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 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.