title: Prednisolone pharmacokinetics in the presence and absence of ritonavir after oral prednisone administration to healthy volunteers.
abstract: 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.
authors.affiliation: Warren G. Magnuson Clinical Center, Pharmacy Department, National Institutes of Health, Bethesda, MD 20892, USA. Spenzak@mail.cc.nih.gov
authors.forename: Scott R
authors.initials: SR
authors.lastname: Penzak
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Formentini
authors.forename: Raul M
authors.initials: RM
authors.lastname: Alfaro
authors.forename: Michael
authors.initials: M
authors.lastname: Long
authors.forename: Ven
authors.initials: V
authors.lastname: Natarajan
authors.forename: Joseph
authors.initials: J
authors.lastname: Kovacs
mesh_terms: 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
chemical_list: D005938:Glucocorticoids; D017320:HIV Protease Inhibitors; D011239:Prednisolone; D019438:Ritonavir