Fosamprenavir with Ritonavir Pharmacokinetics During Pregnancy.

The purpose of this study was to evaluate the pharmacokinetics of ritonavir-boosted fosamprenavir during pregnancy and postpartum. Amprenavir (the active moiety of fosamprenavir) and ritonavir intensive pharmacokinetic evaluations were performed at steady-state during the second and third trimesters of pregnancy and postpartum. Plasma concentrations of amprenavir and ritonavir were measured using high-performance liquid chromatography. Target amprenavir area under the concentration time curve (AUC) was >10th percentile (27.7 μg*hr/mL) of median area under the curve for ritonavir-boosted fosamprenavir in adults receiving twice-daily fosamprenavir/ritonavir, 700mg/100 mg. Twenty-nine women were included in the analysis. Amprenavir AUC0-12 was lower [(geometric mean ratio (GMR) 0.60 (CI 0.49-0.72; p<0.001)] while its apparent oral clearance was higher [(GMR 1.68 (CI 1.38-2.03; p<0.001)] in the third trimester compared to postpartum. Similarly, ritonavir AUC0-12 was lower in the second [GMR 0.51 (CI 0.28-0.91; p=0.09)] and third trimesters [(GMR 0.72 (CI 0.55-0.95; p=0.005)] compared to postpartum, while its apparent oral clearance was higher in the second [GMR 1.98 (CI 1.10-3.56; p=0.06)] and third trimesters [(GMR 1.38 (CI 1.05-1.82; p=0.009)] compared to postpartum. Amprenavir area under the curve exceeded the target for 6/8 (75%) in the 2nd trimester; 18/28 (64%) in the 3rd trimester; and 19/22 (86.4%) postpartum, and the trough concentrations (Cmin) of amprevavir were 4-16 fold above the mean amprenavir-protein-adjusted IC50 of 0.146μg/mL. Although amprenavir plasma concentrations in women receiving ritonavir-boosted fosamprenavir were lower during pregnancy compared to postpartum, the reduced amprenavir concentrations were still above the exposures needed for viral suppression.