Influence of antiretroviral drugs on the pharmacokinetics of prednisolone in HIV-infected individuals

Abstract

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.

FIGURE 1

Median interquartile ranges of prednisolone concentration versus time profiles for 3 HIV-positive groups when administered concurrently with (1) lopinavir/ritonavir, (2) efavirenz, or (3) a control group receiving no ARVs. Bars represent range of data for each group. Solid dots represent outliers from the range of data. LPV/r, lopinavir/ritonavir; EFV, efavirenz; No ARVs, no antiretrovirals.