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Pharmacokinetic and Adrenal Interactions of IL‐10 and Prednisone in Healthy Volunteers
Author(s) -
Chakraborty Abhijit,
Blum Robert A.,
Mis Suzette M.,
Cutler David L.,
Jusko William J.
Publication year - 1999
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912709922008137
Subject(s) - prednisolone , prednisone , pharmacokinetics , crossover study , glucocorticoid , placebo , medicine , hydrocortisone , endocrinology , corticosteroid , pharmacology , chemistry , alternative medicine , pathology
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 C max values were about 3 ng/mL, while the t max occurred 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 significant alterations owing to IL‐10. Both prednisolone and prednisolone/IL‐10 caused marked suppression of cortisol concentrations with similar magnitude and IC 50 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 .