Pharmacokinetic and adrenal interactions of IL-10 and prednisone in healthy volunteers.
The pharmacokinetic and adrenal interactions of recombinant human interleukin-10 and prednisolone were examined in this open-label, randomized, four-way crossover study in 12 healthy adult male volunteers. Single doses of IL-10 (8 micrograms/kg s.c.), IL-10 with prednisone (15 mg p.o.), placebo with prednisone, or placebo were administered on four separate occasions with at least 3-week interceding washout periods. Measurements included plasma prednisone, prednisolone and cortisol, unbound prednisolone, and serum IL-10 concentrations. Pharmacokinetic parameters were determined using noncompartmental and model-fitting analysis, while area analysis and an indirect response model were used to assess cortisol dynamics. IL-10 exhibited prolonged serum concentrations owing to dual-absorption processes that were largely unaffected by prednisone. The Cmax values were about 3 ng/mL, while the tmax occurred at 7 to 9 hours. Prednisolone exhibited rapid systemic kinetics with a Cmax of 235 ng/mL, tmax at 1.11 hours, and t1/2 of 2.54 hours with no significant alterations owing to IL-10. Both prednisolone and prednisolone/IL-10 caused marked suppression of cortisol concentrations with similar magnitude and IC50 values; however, IL-10 alone significantly increased the 24-hour AUC of cortisol by 20%. Thus, IL-10 and prednisolone do not interact in disposition or adrenal suppression to a clinically significant degree.
Chakraborty
A
A
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo 14260, USA.
Blum
R A
RA
Mis
S M
SM
Cutler
D L
DL
Jusko
W J
WJ
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D016753:Interleukin-10 / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D011241:Prednisone / Q000493:pharmacokinetics*
D000893:Anti-Inflammatory Agents; D016753:Interleukin-10; D011241:Prednisone; D006854:Hydrocortisone