Pharmacokinetics of saquinavir-SGC in HIV-infected pregnant women

Abstract

Purpose: To evaluate saquinavir (SQV) pharmacokinetics, tolerance, and safety in 10 HIV-infected pregnant women between 14-32 weeks gestation.

Method: This was a phase I, prospective, area-under-the-curve (AUC) targeted study. Antepartum treatment consisted of SQV 1200 mg tid, lamivudine 150 mg bid, and zidovudine 200 mg tid. The SQV targeted exposure was an 8-hour AUC (AUC(8)) of 3000 ng. h/mL; the study was to be halted if the first 4 participants did not achieve this AUC(8). Cord blood and plasma samples were collected in neonates at birth.

Results: Four women completed the SQV pharmacokinetic assessments. Exposure in all 4 patients was below the target AUC(8). Median (range) AUC(8) and trough (C8H) were 1672 (738-2614) ng. h/mL and 60 (<15-332) ng/mL, respectively. Oral clearance (CL/F) was 9.3 (5.1-16.6) L/h/kg and C(max) was 599 (177-953) ng/mL. Cord and neonate plasma concentrations were mostly undetectable; 1 of 5 infants was HIV-infected at 24 weeks.

Conclusion: These data suggest highly variable SQV pharmacokinetics in pregnant women, and exposure at 1200 mg tid may not be adequate for longer term therapy; both the AUC(8) and C8H were considerably below average. Because ritonavir has been shown to significantly increase SQV concentrations, this combination should be further explored in this population.