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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >A pharmacokinetic study of intramuscular (i.m.) parecoxib sodium in normal subjects.
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A pharmacokinetic study of intramuscular (i.m.) parecoxib sodium in normal subjects.

机译：在正常受试者中肌内（i.m.）帕瑞昔布钠的药代动力学研究。

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A single-center, double-blind, placebo-controlled, randomized study was conducted to determine the pharmacokinetics, safety, and tolerability of single, rising intramuscular (i.m.) 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. Cohorts 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 i.m. 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 i.m. 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) = 5.4-9.9 hours), reflected transformation to several metabolites, one of which was the minor active metabolite M1. As measured by the AUC(0-infinity), Cmax, and XU(0-24) of valdecoxib, parecoxib sodium demonstrated dose proportionality when administered in the range of 1 mg to 40 mg of parecoxib. All single i.m. doses up to the maximum of 40 mg of parecoxib, as well as concentrations of up to 20 mg/ml, were well tolerated.
机译：进行了一项单中心，双盲，安慰剂对照的随机研究，以确定单次上升的肌内（im）剂量和帕瑞昔布钠的单次最大耐受剂量（新药的前药）的药代动力学，安全性和耐受性在56名年龄在18至45岁（包括15岁）的健康男性志愿者中，COX-2选择性抗炎镇痛药valdecoxib。在每个剂量方案中，最多6名受试者的组被给予帕瑞昔布钠（1 mg，2 mg，5 mg，10 mg，20 mg或40 mg）或匹配的安慰剂。在我之后给药时，以预定的时间间隔（给药前15分钟至给药后96小时）收集用于测定帕瑞昔布，伐地昔布和伐地昔布代谢物（M1）血浆浓度的系列血样。获得尿液收集物用于药物测定（给药后-12至0小时，0至12小时和12至24小时）。在我之后给药后，帕瑞昔布的血浆峰值浓度在15分钟内达到峰值，然后随着前药转化为活性成分伐地昔布而迅速下降。伐地考昔的血浆浓度变化缓慢下降（t（1/2）= 5.4-9.9小时），反映了向几种代谢物的转化，其中一种是次要的活性代谢物M1。如通过伐地昔布的AUC（0-无穷大），Cmax和XU（0-24）测量，帕瑞昔布钠在帕瑞昔布1 mg至40 mg范围内给药时显示出剂量比例性。所有单身最高耐受剂量为40 mg派瑞昔布，最高浓度为20 mg / ml，耐受性良好。

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