Pharmacokinetics and Safety of Indinavir in Human Immunodeficiency Virus-Infected Pregnant Women

Author:

Unadkat Jashvant D.1,Wara Diane W.2,Hughes Michael D.3,Mathias Anita A.1,Holland Diane T.4,Paul Mary E.5,Connor James4,Huang Sharon3,Nguyen Bach-Yen6,Watts D. Heather7,Mofenson Lynne M.7,Smith Elizabeth8,Deutsch Paul6,Kaiser Kathleen A.9,Tuomala Ruth E.10

Affiliation:

1. Department of Pharmaceutics, University of Washington, Seattle, Washington

2. Department of Pediatrics, University of California San Francisco, San Francisco, California

3. Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts

4. Division of Clinical Pharmacology and Developmental Therapeutics, University of California, San Diego, California

5. Baylor College of Medicine, Houston, Texas

6. Merck Research Laboratories, West Point, Pennsylvania

7. Pediatric Adolescent and Maternal AIDS Branch, National Institute of Child Health and Human Development, Bethesda, Maryland

8. Pediatric Medical Branch, Therapeutics Research Plan, Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland

9. Frontier Science and Technology Research Foundation

10. Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts

Abstract

ABSTRACT Human immunodeficiency virus-infected women ( n = 16) received indinavir (800 mg three times a day) plus zidovudine plus lamivudine from 14 to 28 weeks of gestation to 12 weeks postpartum. Two women and eight infants experienced grade 3 or 4 toxicities that were possibly treatment related. Indinavir area under the plasma concentration-time curve was 68% lower antepartum versus postpartum, suggesting increased intestinal and/or hepatic CYP3A activity during pregnancy.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference13 articles.

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4. Centers For Disease Control and Prevention. 1998. Public Health Service Task Force recommendations for the use of antiretroviral drugs in pregnant women infected with HIV-1 for maternal health and for reducing perinatal HIV-1 transmission in the United States. Morb. Mortal. Wkly. Rep.47:1-20.

5. Choo, E. F., B. Leake, C. Wandel, H. Imamura, A. J. Wood, G. R. Wilkinson, and R. B. Kim. 2000. Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab. Dispos.28:655-660.

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