Document Detail

Pharmacokinetics of nelfinavir and indinavir in HIV-1-infected pregnant women.
MedLine Citation:
PMID:  12819521     Owner:  NLM     Status:  MEDLINE    
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 (AUC(tau)), 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 6 beta-hydroxycortisol to cortisol ratio (6 beta-OHF/F). RESULTS: AUC(tau) in women on indinavir alone decreased and 6 beta-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.
Bradley W Kosel; Karen P Beckerman; Sandra Hayashi; Masato Homma; Francesca T Aweeka
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  AIDS (London, England)     Volume:  17     ISSN:  0269-9370     ISO Abbreviation:  AIDS     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-06-23     Completed Date:  2003-07-31     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  1195-9     Citation Subset:  IM; X    
Drug Research Unit, Department of Clinical Pharmacy, University of California, San Francisco, 94143, USA.
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MeSH Terms
Gestational Age
HIV Infections / blood*,  urine,  virology
HIV Protease Inhibitors / blood*
Hydrocortisone / analogs & derivatives*,  urine
Indinavir / blood
Nelfinavir / blood
Pregnancy Complications, Infectious / blood*,  urine,  virology
Viral Load
Grant Support
Reg. No./Substance:
0/HIV Protease Inhibitors; 150378-17-9/Indinavir; 159989-64-7/Nelfinavir; 50-23-7/Hydrocortisone; 53-35-0/6 beta-hydroxycortisol

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