SEARCH

SEARCH BY CITATION

Keywords:

  • HIV;
  • nelfinavir;
  • pharmacokinetics;
  • pregnancy

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 (AUC0–12) was ≥10th percentile NFV AUC0–12 in non-pregnant historical controls (18.5 μg h/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 (Cmax), 12-h post-dose concentration (C12) and AUC0–12 were significantly lower during the third trimester compared to postpartum (P≤0.03). The metabolite hydroxyl-tert-butylamide (M8) AUC0–12 and the M8/NFV AUC ratio were lower during the third trimester compared to postpartum (P<0.01). The NFV AUC0–12 exceeded the AUC0–12 target for 15/27 (56%) and 21/22 (95%) of third trimester and postpartum patients, respectively. The minimum concentration (Cmin) was above the suggested minimum trough concentration (0.8 μg/mL) in 15% (third trimester) and 18% (postpartum). The plasma viral load was <400 HIV-1 RNA copies/mL in 81% of patients at delivery.

Conclusions

These results suggest that higher doses of NFV should be considered during pregnancy.