A pharmacokinetic study of intramuscular (IM) parecoxib sodium in normal subjects

被引:62
作者
Karim, A
Laurent, A
Slater, ME
Kuss, ME
Qian, J
Crosby-Sessoms, SL
Hubbard, RC
机构
[1] Pharmacia, Res & Dev, Skokie, IL 60077 USA
[2] PPD Dev, Austin, TX USA
关键词
D O I
10.1177/00912700122012607
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A single-center, double-blind, placebo-controlled, randomized study was conducted to determine the pharmacokinetics, safety, and tolerability of single, rising intramuscular (IM) doses and the single maximum tolerated dose of parecoxib sodium, a prodrug of the novel COX-2 selective anti-inflammatory analgesic drug valdecoxib, in 56 healthy male volunteers, ages 18 to 45 years inclusive. Coports of up to 6 subjects in each dose schedule were administered either parecoxib sodium (1 mg, 2 mg, 5 mg, 10 mg, 20 mg, or 40 mg) or matching placebo. Following 1M administration, serial blood samples for measurement of plasma concentrations of parecoxib, valdecoxib, and valdecoxib metabolite (M1) were collected at predetermined intervals (from 15 minutes prior to dose and through 96 hours postdose). Urine collections were obtained for drug assay (from -12 to 0 hours, 0 to 12 hours, and 12 to 24 hours postdose). After 1M administration, peak plasma concentrations of parecoxib were reached within 15 minutes and then declined rapidly as prodrug was converted to the active moiety, valdecoxib. Change in plasma concentrations of valdecoxib, which declined more slowly(t(1/2)=5.4-9.9hours),reflected transformation to several metabolites, one of which was the minor active metabolite M1. As measured by the AUC(0-infinity) C-max, and XU0-24 of valdecoxib, parecoxib sodium demonstrated dose proportionality when administered in the range of 1 mg to 40 mg of parecoxib. All single IM doses up to the maximum of 40 mg of parecoxib, as well as concentrations of up to 20 mg/ml, were well tolerated. (C) 2001 the American College of Clinical Pharmacology.
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页码:1111 / 1119
页数:9
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