Pharmacokinetics of new 625mg nelfinavir formulation during pregnancy and postpartum

Objectives: Our objective was to evaluate the pharmacokinetics of nelfinavir (NFV) (625 mg tablets) 1250 mg twice daily during pregnancy and postpartum. Methods: The participants were HIV-1-infected pregnant women enrolled in P1026s and receiving NFV (625 mg tablets) 1250 mg twice daily as part of routine clinical care. Intensive steady-state 12-h NFV pharmacokinetic profiles were performed during pregnancy and postpartum. The target NFV area under the plasma concentration-time curve (AUC_0-12) was ≥ 10th percentile NFV AUC_0-12 in non-pregnant historical controls (18.5 μgh/mL). Results: Of 27 patients receiving NFV, pharmacokinetic data were available for four (second trimester), 27 (third trimester) and 22 (postpartum) patients. The NFV maximum concentration (C_max), 12-h post-dose concentration (C₁₂) and AUC_0-12 were significantly lower during the third trimester compared to postpartum (P ≤ 0.03). The metabolite hydroxyl-tert-butylamide (M8) AUC_0-12 and the M8/NFV AUC ratio were lower during the third trimester compared to postpartum (P < 0.01). The NFV AUC_0-12 exceeded the AUC_0-12 target for 15/27 (56%) and 21/22 (95%) of third trimester and postpartum patients, respectively. The minimum concentration (C_min) was above the suggested minimum trough concentration (0.8 μg/mL) in 15% (third trimester) and 18% (postpartum). The plasma viral load was < 400HIV-1 RNAcopies/mL in 81% of patients at delivery. Conclusions: These results suggest that higher doses of NFV should be considered during pregnancy.