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Pharmacokinetic interaction between nelfinavir and pravastatin in HIV-seronegative volunteers: ACTG Study A5108

Aberg, Judith Aa; Rosenkranz, Susan Lb; Fichtenbaum, Carl Jc; Alston, Beverly Ld; Brobst, Susan We; Segal, Yoninahb; Gerber, John Gf; for the ACTG A5108 team

doi: 10.1097/01.aids.0000216373.53819.92
Clinical Science: Concise Communication

Background: Nelfinavir, an HIV protease inhibitor with numerous drug–drug interactions, is associated with dyslipidemia. Pravastatin is the preferred statin prescribed for HIV-associated dyslipidemia.

Objective: To examine the effect of nelfinavir on pravastatin pharmacokinetics.

Design: Open-label study in healthy HIV-seronegative adults conducted at the AIDS Clinical Trials Group sites in the United States.

Methods: Subjects received pravastatin 40 mg daily and underwent intensive sampling for pharmacokinetics on day 3. Subjects took only nelfinavir 1250 mg twice daily on days 4–12. On days 13–15, subjects continued nelfinavir and reinitiated pravastatin. Plasma samples were collected over 24 h for the calculation of pravastatin area under the concentration–time curve for 0–24 h on days 3 and 16.

Results: Data from 14 subjects with complete pharmacokinetic samples were available for analysis. The median within-subject percentage change in pravastatin AUC was a decrease of 46.5%. Pravastatin maximum plasma concentrations were also lower when pravastatin was administered with nelfinavir. Median values for the maximum plasma concentrations were 27.9 and 12.4 ng/ml for days 3 and 16, respectively, and the median within-subject decrease was 40.1%.

Conclusions: Coadministration of pravastatin and nelfinavir led to a substantial reduction in pravastatin plasma concentrations. Higher doses of pravastatin may need to be prescribed in order to achieve optimal lipid-lowering activity.

From the aNew York University, New York, New York

bHarvard School of Public Health, Boston, Massachusetts

cUniversity of Cincinnati, Cincinnati, Ohio

dNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

eSocial and Scientific Systems, Inc., Silver Spring, Maryland

fUniversity of Colorado Health Sciences Center, Denver, Colorado, USA.

*See Appendix.

Received 24 September, 2005

Revised 14 November, 2005

Accepted 30 November, 2005

Correspondence to Dr J. Aberg, New York University, Bellevue C and D Building, Room 558, 550 First Ave, New York, New York 10016–6481, USA. E-mail: judith.aberg@med.nyu.edu

© 2006 Lippincott Williams & Wilkins, Inc.