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

被引:21
作者
Chakraborty, A [1 ]
Blum, RA
Mis, SM
Cutler, DL
Jusko, WJ
机构
[1] SUNY Buffalo, Dept Pharmaceut, Sch Pharm, Buffalo, NY 14260 USA
[2] Millard Fillmore Hosp, Clin Pharmacokinet Lab, Buffalo, NY 14209 USA
[3] Schering Plough Res Inst, Kenilworth, NJ USA
关键词
D O I
10.1177/00912709922008137
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 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-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 prednisolane 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, (C) 1999 the American College of Clinical Pharmacology.
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页码:624 / 635
页数:12
相关论文
共 27 条
[1]   Pharmacoimmunodynamic interactions of interleukin-10 and prednisone in healthy volunteers [J].
Chakraborty, A ;
Blum, RA ;
Cutler, DL ;
Jusko, WJ .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1999, 65 (03) :304-318
[2]  
CHAKRABORTY A, 1998, PHARMSCI S, V1, pS234
[3]  
D'Argenio D, 1997, PHARMACOKINETIC PHAR
[4]   COMPARISON OF 4 BASIC MODELS OF INDIRECT PHARMACODYNAMIC RESPONSES [J].
DAYNEKA, NL ;
GARG, V ;
JUSKO, WJ .
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS, 1993, 21 (04) :457-478
[5]  
DEVENTER SJH, 1997, GASTROENTEROLOGY, V113, P383
[6]   IMMUNOSUPPRESSIVE AND ANTIINFLAMMATORY PROPERTIES OF INTERLEUKIN-10 [J].
DEVRIES, JE .
ANNALS OF MEDICINE, 1995, 27 (05) :537-541
[7]   EFFECT OF THE ANTIINFLAMMATORY AGENT TENIDAP ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF PREDNISOLONE [J].
GARG, V ;
BLUM, R ;
WILNER, KD ;
JUSKO, WJ .
JOURNAL OF CLINICAL PHARMACOLOGY, 1992, 32 (03) :222-230
[8]   SIMULTANEOUS ANALYSIS OF PREDNISONE, PREDNISOLONE AND THEIR MAJOR HYDROXYLATED METABOLITES IN URINE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY [J].
GARG, V ;
JUSKO, WJ .
JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS, 1991, 567 (01) :39-47
[9]  
Haehner-Daniels BD, 1998, CLIN PHARMACOL THER, V63, P241
[10]   Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers [J].
Huhn, RD ;
Radwanski, E ;
OConnell, SM ;
Sturgill, MG ;
Clarke, L ;
Cody, RP ;
Affrime, MB ;
Cutler, DL .
BLOOD, 1996, 87 (02) :699-705