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 (AUC8) of 3000 ng · h/mL; the study was to be halted if the first 4 participants did not achieve this AUC8. 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 AUC8. Median (range) AUC8 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 Cmax 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 AUC8 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.
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