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The pharmacokinetics of nelfinavir and M8 during pregnancy and post partum
Journal article   Peer reviewed

The pharmacokinetics of nelfinavir and M8 during pregnancy and post partum

R. Heeswijk, Y. Khaliq, K. Gallicano, M. Bourbeau, I. Seguin, E. Phillips and D. Cameron
Clinical Pharmacology & Therapeutics, Vol.76(6), pp.588-597
2004
DOI: https://doi.org/10.1016/j.clpt.2004.08.011
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Abstract

Objective: The objective of this study was to explore the pharmacokinetics of nelfinavir and its active metabolite hydroxy-t-butylamidenelfinavir (M8) during pregnancy and post partum. Methods: Eleven human immunodeficiency virus type 1–infected pregnant women receiving 1250 mg nelfinavir twice daily were enrolled. Pharmacokinetics of nelfinavir and M8 were assessed over a 12-hour period during pregnancy (median, 32 weeks' gestation; range, 31-36 weeks) and post partum (median, 8 weeks post partum; range, 6-15 weeks). Drug concentrations were analyzed by HPLC coupled to tandem mass spectroscopy, and pharmacokinetic parameters were calculated by use of noncompartmental methods. Results: The median area under the plasma concentration–time curve from 0 to 12 hours (AUC0-12), the maximal plasma concentration (Cmax), and the concentration at the end of the dosing interval (C12) for nelfinavir post partum were 33.5 h · μg/mL, 5.80 μg/mL, and 1.40 μg/mL, respectively. The values for the geometric mean ratio (GMR) (third trimester/post partum) for the nelfinavir AUC0-12, Cmax, and C12 were 0.76 (90% confidence interval [CI], 0.54-1.06), 0.81 (90% CI, 0.57-1.15), and 0.43 (90% CI, 0.25-0.76), respectively. The GMR values for the M8 AUC0-12, Cmax, and C12 were 0.32 (90% CI, 0.18-0.55), 0.31 (90% CI, 0.19-0.51), and 0.30 (90% CI, 0.14-0.64), respectively. The median ratio values of the AUC0-12 of M8 and nelfinavir (M8/nelfinavir) during the third trimester and post partum were 11% and 27%, respectively (GMR, 0.42 [90% CI, 0.33-0.53]). Conclusions: Nelfinavir exposure was reduced during pregnancy, and the reduction was statistically significant for C12. M8 concentrations were about 70% lower during pregnancy compared with post partum, suggesting either induction of hepatic cytochrome P450 (CYP) 3A4 or inhibition of CYP2C19, or both, during pregnancy. Because 8 of 11 women had subtherapeutic nelfinavir trough concentrations during pregnancy, the safety and efficacy of therapeutic drug monitoring should be investigated.

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Collaboration types
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.66 HIV
1.66.1372 HIV Comorbidities
Web Of Science research areas
Pharmacology & Pharmacy
ESI research areas
Pharmacology & Toxicology
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