Pharmacokinetic and adrenal interactions of IL-10 and prednisone in healthy volunteers

The pharmacokinetic and adrenal interactions of recombinant human interleuk in-10 and prednisolone were examined in this open-label, randomized four-wa y crossover study in 12 healthy adult male volunteers. Single doses of IL-1 0 (8 mu g/kg SC), IL-10 with prednisone (15 mg PO), placebo with prednisone , or placebo were administered on four separate occasions with at least 3-w eek interceding washout periods. Measurements included plasma prednisone, p rednisolone and cortisol, unbound prednisolone, and serum IL-10 concentrati ons. 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 conc entrations owing to dual-absorption processes that were largely unaffected by prednisone. The C-max values were about 3 ng/ml, while the t(max) occurr ed at 7 to 9 hours. Prednisolone exhibited rapid systemic kinetics with a C -max of 235 ng/mL, t(max) at 1.11 hours, and t(1/2) of 2.54 hours with no s ignificant alterations owing to IL-10. Both prednisolane and prednisolone/I L-10 caused marked suppression of cortisol concentrations with similar magn itude 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 i n disposition or adrenal suppression to a clinically significant degree, (C ) 1999 the American College of Clinical Pharmacology.