期刊
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
卷 48, 期 5, 页码 561-566出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAI.0b013e31817bebeb
关键词
drug interaction; cytochrome P450; nonnucleoside reverse transcriptase inhibitor; protease inhibitor; corticosteroid
资金
- Intramural NIH HHS [Z01 CL005096-05] Funding Source: Medline
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.
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