Presented in part at the 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, CA, February 2007 [Abstract 740].
Pharmacokinetics of new 625 mg nelfinavir formulation during pregnancy and postpartum
Article first published online: 14 SEP 2008
No claim to original US government works
Volume 9, Issue 10, pages 875–882, November 2008
How to Cite
Read, J., Best, B., Stek, A., Hu, C., Capparelli, E., Holland, D., Burchett, S., Smith, M., Sheeran, E., Shearer, W., Febo, I. and Mirochnick, M. (2008), Pharmacokinetics of new 625 mg nelfinavir formulation during pregnancy and postpartum. HIV Medicine, 9: 875–882. doi: 10.1111/j.1468-1293.2008.00640.x
- Issue published online: 27 OCT 2008
- Article first published online: 14 SEP 2008
- Received: 8 February 2008, accepted 5 June 2008
Our objective was to evaluate the pharmacokinetics of nelfinavir (NFV) (625 mg tablets) 1250 mg twice daily during pregnancy and postpartum.
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).
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.
These results suggest that higher doses of NFV should be considered during pregnancy.