Pharmacokinetic and Adrenal Interactions of IL‐10 and Prednisone in Healthy Volunteers

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Abstract
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 μg/kg SC), IL‐10 with prednisone (15 mg PO), 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.