Prednisolone pharmacokinetics in the presence and absence of ritonavir after oral prednisone administration to healthy volunteers.
Corticosteroid therapy has been associated with bone toxicities (eg, osteonecrosis) and Cushing syndrome in HIV-infected patients; this may be partially attributable to a pharmacokinetic drug interaction between HIV protease inhibitors and corticosteroids. The purpose of this study was to characterize the influence of low-dose ritonavir on prednisolone pharmacokinetics in healthy subjects. Ten HIV-seronegative volunteers were given single oral doses of prednisone, 20 mg, before (baseline) and after receiving ritonavir, 200 mg, twice daily for 4 and 14 days. After each prednisone dose, serial blood samples were collected and prednisolone concentrations were determined; pharmacokinetic parameter values were compared between the groups. Geometric mean ratios (GMRs, 90% confidence interval [CI]) of the prednisolone area under the plasma concentration versus time curve (AUC0-infinity) after 4 and 14 days of ritonavir versus baseline were 1.41 (90% CI: 1.08 to 1.74) and 1.30 (90% CI: 1.09 to 1.49), respectively (P = 0.002 and P = 0.004, respectively). GMRs of prednisolone apparent oral clearance (Cl/F) were 0.71 (09% CI: 0.57 to 0.93) and 0.77 (90% CI: 0.67 to 0.92) after 4 and 14 days of ritonavir versus baseline, respectively (P = 0.0004 and P = 0.0003, respectively). Ritonavir significantly increased the systemic exposure of prednisolone in healthy subjects. Results from this investigation suggest that corticosteroid exposure is likely elevated in HIV-infected patients receiving protease inhibitors.
Penzak
Scott R
SR
Warren G. Magnuson Clinical Center, Pharmacy Department, National Institutes of Health, Bethesda, MD 20892, USA. Spenzak@mail.cc.nih.gov
Formentini
Elizabeth
E
Alfaro
Raul M
RM
Long
Michael
M
Natarajan
Ven
V
Kovacs
Joseph
J
D000328:Adult; D019540:Area Under Curve; D004347:Drug Interactions; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D018023:HIV Seronegativity; D006801:Humans; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology
D005938:Glucocorticoids; D017320:HIV Protease Inhibitors; D011239:Prednisolone; D019438:Ritonavir