Pharmacokinetics of nelfinavir and indinavir in HIV-1-infected pregnant women

Bradley W. Kosel, Karen P. Beckerman, Sandra Hayashi, Masato Homma, Francesca T. Aweeka

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Background: Protease inhibitor (PI)-based combination antiretroviral therapy is often indicated for treatment of maternal HIV disease, but little is known about PI pharmacokinetics during pregnancy. Increased cytochrome P450 activity may affect the disposition of PI and decrease drug exposure. Methods: Steady-state PI pharmacokinetics, measured by the area under the plasma concentration versus time curve (AUCtau), were evaluated in women on stable antiretroviral regimens containing nelfinavir (n = 9) or indinavir (n = 4) with or without ritonavir (n = 2) during the second and third trimesters of pregnancy and postpartum. Cytochrome P450 activity was assessed by measuring the urine 6β-hydroxycortisol to cortisol ratio (6β-OHF/F). Results: AUCtau in women on indinavir alone decreased and 6β-OHF/F ratios increased during pregnancy compared with postpartum control values (n = 2). Nelfinavir results demonstrated no clear change and were highly variable. Conclusions: The results for indinavir suggest that metabolic induction occurs during pregnancy, which apparently resolves spontaneously postpartum. This may warrant dosage adjustment during pregnancy. This induction is offset by concomitant use of ritonavir. Nelfinavir results were variable and, therefore, the impact of pregnancy on nelfinavir disposition was not fully determined.

Original languageEnglish
Pages (from-to)1195-1199
Number of pages5
JournalAIDS
Volume17
Issue number8
DOIs
StatePublished - 23 May 2003
Externally publishedYes

Keywords

  • HIV protease inhibitors
  • HIV-1
  • Indinavir
  • Nelfinavir
  • Pharmacokinetics
  • Pregnancy
  • Women

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