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

IMPAACT P1026s Protocol Team

Research output: Contribution to journalArticle

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 AUC 0–12 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.

Original languageEnglish (US)
Pages (from-to)386-393
Number of pages8
JournalJournal of clinical pharmacology
Volume59
Issue number3
DOIs
StatePublished - Mar 1 2019

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Nelfinavir
Third Pregnancy Trimester
Postpartum Period
Pharmacokinetics
Pregnancy
HIV
Safety
Ritonavir
Protease Inhibitors
Hydroxyl Radical
Pregnant Women
Acquired Immunodeficiency Syndrome
Cohort Studies
High Pressure Liquid Chromatography
Mothers
Clinical Trials
Prospective Studies
Pediatrics

Keywords

  • hydroxyl-tert-butylamide
  • nelfinavir
  • postpartum
  • pregnancy

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Pharmacokinetics of Increased Nelfinavir Plasma Concentrations in Women During Pregnancy and Postpartum. / IMPAACT P1026s Protocol Team.

In: Journal of clinical pharmacology, Vol. 59, No. 3, 01.03.2019, p. 386-393.

Research output: Contribution to journalArticle

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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 AUC 0–12 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.",
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