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Influence of Antiretroviral Drugs on the Pharmacokinetics of Prednisolone in HIV-Infected Individuals

Busse, Kristin H PharmD*; Formentini, Elizabeth RNC, MSN, FNP-C; Alfaro, Raul M MS*; Kovacs, Joseph A MD; Penzak, Scott R PharmD, FCP*

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 15th, 2008 - Volume 48 - Issue 5 - p 561-566
doi: 10.1097/QAI.0b013e31817bebeb
Clinical Science

Background: Corticosteroids are cytochrome P450 3A4 substrates, which have been associated with toxicities in patients receiving cytochrome P450 3A4 inhibitors such as human immunodeficiency virus protease inhibitors. In a study in healthy volunteers, ritonavir significantly increased prednisolone exposure.

Methods: We investigated the influence of antiretroviral (ARV) medications on prednisolone pharmacokinetics in 3 groups of 10 human immunodeficiency virus-infected subjects. One group received lopinavir/ritonavir, and another efavirenz, as part of their ARV regimen; a third group did not receive ARV medications. Each subject received a single 20-mg prednisone dose followed by serial blood sampling for prednisolone. Prednisolone pharmacokinetics were compared among the groups.

Results: Area under the concentration-time curve was significantly lower in efavirenz recipients versus subjects receiving lopinavir/ritonavir (geometric mean ratio = 0.60, P = 0.01). Average prednisolone area under the concentration-time curve was higher in subjects taking lopinavir/ritonavir versus subjects not on ARVs; however, this difference was not significant (P > 0.05).

Conclusions: These data indicate that prednisolone concentrations may fluctuate widely when human immunodeficiency virus-positive individuals established on efavirenz therapy change to lopinavir/ritonavir or vice versa.

From the *Pharmacy Department; and †Department of Critical Care Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD.

Received for publication November 13, 2007; accepted April 2, 2008.

Supported by the National Institutes of Health Clinical Center Pharmacy Department and the National Institute of Allergy and Infectious Diseases.

Correspondence to: Scott Penzak, PharmD, FCP, National Institutes of Health Clinical Center Pharmacy Department, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 1N-257, Bethesda, MD 20896-1196 (e-mail: spenzak@cc.nih.gov).

© 2008 Lippincott Williams & Wilkins, Inc.