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J Clin Pharmacol. 2019 Mar;59(3):386-393. doi: 10.1002/jcph.1331. Epub 2018 Oct 25.

Pharmacokinetics of Increased Nelfinavir Plasma Concentrations in Women During Pregnancy and Postpartum.

Author information

1
Division of Maternal Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2
University of California San Diego School of Medicine, San Diego, CA, USA.
3
University of California San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA, USA.
4
University of Southern California School of Medicine, Los Angeles, CA, USA.
5
Harvard School of Public Health, Center for Biostatistics in AIDS Research, Boston, MA, USA.
6
Irmandade da Santa Casa de Misericórdia de Porto Alegre, HIV/AIDS Research Department, Porto Alegre, Rio Grande do Sul, Brazil.
7
National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.
8
National Institute of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD, USA.
9
Boston University School of Medicine, Boston, MA, USA.

Abstract

This study aims to evaluate the safety, acceptability, and pharmacokinetics (PK) of an increased dose of nelfinavir (NFV) during the third trimester of pregnancy. The study was registered as part of the International Maternal Pediatric Adolescent AIDS Clinical Trials network (IMPAACT-P1026s), an ongoing multicenter prospective cohort study of antiretroviral PK during pregnancy (NCT00042289). NFV intensive PK evaluations were performed at steady state during the third trimester of pregnancy and 2-3 weeks postpartum. Plasma concentrations of NFV and its active metabolite, hydroxyl-tert-butylamide (M8) were measured using high-performance liquid chromatography with ultraviolet detection. A total of 18 women are included in the analysis. NFV area under the concentration-time curve (AUC) with the increased dose during the third trimester was nearly identical to the standard dose postpartum, with a geometric mean ratio for third trimester to postpartum AUC of 0.98 (90%CI 0.71-1.35). Despite the increased dose, M8 AUC was lower during the third trimester compared to postpartum (0.53, IQR [0.38-0.75]), as was the M8/NFV AUC ratio (0.51, IQR [0.42-0.63]). NFV AUC0-12 was above target in 15 of 18 (83%) of participants during the third trimester compared to 14 of 16 (88%) postpartum. No major safety concerns were noted. Increasing the NFV dose to 1875 mg twice daily during the third trimester achieved similar concentrations postpartum compared to standard dosing (1250 mg twice daily). Increased NFV dose regimens may still have some benefit to human immunodeficiency virus (HIV)-positive pregnant women living in countries where novel protease inhibitors are currently unavailable or in individuals who are intolerant to ritonavir-boosted HIV medications.

KEYWORDS:

hydroxyl-tert-butylamide; nelfinavir; postpartum; pregnancy

PMID:
30358179
PMCID:
PMC6368469
[Available on 2020-03-01]
DOI:
10.1002/jcph.1331

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