TY - JOUR
T1 - Prednisolone pharmacokinetics in the presence and absence of ritonavir after oral prednisone administration to healthy volunteers
AU - Penzak, Scott R.
AU - Formentini, Elizabeth
AU - Alfaro, Raul M.
AU - Long, Michael
AU - Natarajan, Ven
AU - Kovacs, Joseph
PY - 2005/12
Y1 - 2005/12
N2 - 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-∞) 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.
AB - 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-∞) 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.
KW - Corticosteroid
KW - Cytochrome P450
KW - Drug interaction
KW - Protease inhibitor
UR - http://www.scopus.com/inward/record.url?scp=27944433384&partnerID=8YFLogxK
U2 - 10.1097/01.qai.0000187444.38461.70
DO - 10.1097/01.qai.0000187444.38461.70
M3 - Article
C2 - 16284534
AN - SCOPUS:27944433384
VL - 40
SP - 573
EP - 580
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
SN - 1525-4135
IS - 5
ER -