塞来昔布在健康泰国志愿者中的临床药代动力学。

Clinical pharmacokinetic of celecoxib in healthy Thai volunteers.

作者信息

Itthipanichpong Chandhanee, Chompootaweep Sumana, Wittayalertpanya Supeecha, Kemsri Wandee, Thaworn Nongnuch, Lilitkarntrakul Pajaree, Parikamsil Sithiporn

机构信息

Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

出版信息

J Med Assoc Thai. 2005 May;88(5):632-8.

PMID:16149679

Abstract

BACKGROUND

Celecoxib, a nonsteroidal antiinflammatory drug exhibits its antiinflammatory effect by selective inhibition of cyclooxygenase-2 (COX-2) enzyme. Its efficacy has been accepted for the treatment of arthritic pain with superior gastrointestinal side effect profile compared with other conventional NSAIDs.

OBJECTIVE

To elucidate clinical pharmacokinetic of celecoxib following an oral dose administration.

MATERIAL AND METHOD

Eighteen healthy Thai male volunteers were enrolled in the present study. Their mean age was 20.94 +/- 1.21 years and their mean weight was 63 +/- 5.17 kg. They were orally administered 200 mg celecoxib after an over night fasting, serial blood samples were drawn before and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours after dosing. Plasma celecoxib was analysed by reversed-phase HPLC.

RESULTS

Following a 200 mg celecoxib oral administration, the drug was absorbed into the systemic circulation and reach maximum concentration (Tmax) within 2.50 +/- 1.22 hrs by average with the mean peak concentration (Cmax) of 686.83 +/- 211.35 ng/ml. The extent of absorption (area under the curve, AUC) was approximately 5157.12 +/- 1499.46 and 5911.48 +/- 1363.51 ng hr/ml for AUC(0-->t) and AUC(0-->infinity) respectively. The apparent volume of distribution (Vd) was found to be 458.93 +/- 323.28 L/hr. Celecoxib was eliminated after biotransformation and the metabolites were excreted in both urine and feces. The elimination half-life (t(1/2)) of celecoxib appeared to be 8.79 +/- 5.49 hrs with the apparent clearance (CL) of 35.91 +/- 9.85 L. The elimination rate constant for celecoxib obtained from this present study was about 0.11 +/- 0.05 hr(-1).

CONCLUSION

Pharmacokinetic parameters following an oral dose of 200 mg celecoxib administration were characterized, including Cmax, Tmax, Vd, kel, CL, AUC. These parameters reflected absorption, distribution, biotransformation and excretion of celecoxib in healthy Thai volunteers.

摘要

背景

塞来昔布是一种非甾体抗炎药，通过选择性抑制环氧化酶 - 2（COX - 2）发挥抗炎作用。与其他传统非甾体抗炎药相比，其治疗关节炎疼痛的疗效已得到认可，且胃肠道副作用较小。

目的

阐明口服给药后塞来昔布的临床药代动力学。

材料与方法

本研究纳入了18名健康的泰国男性志愿者。他们的平均年龄为20.94±1.21岁，平均体重为63±5.17千克。经过一夜禁食后，他们口服200毫克塞来昔布，给药前及给药后0.5、1、1.5、2、2.5、3、3.5、4、5、6、8、10、12、24和48小时采集系列血样。采用反相高效液相色谱法分析血浆中的塞来昔布。

结果

口服200毫克塞来昔布后，药物被吸收进入体循环，平均在2.50±1.22小时内达到最大浓度（Tmax），平均峰浓度（Cmax）为686.83±211.35纳克/毫升。吸收程度（曲线下面积，AUC），AUC(0→t)约为5157.12±1499.46纳克·小时/毫升，AUC(0→∞)约为5911.48±1363.51纳克·小时/毫升。表观分布容积（Vd）为458.93±323.28升/小时。塞来昔布经生物转化后被消除，代谢产物经尿液和粪便排出。塞来昔布的消除半衰期（t(1/2)）约为8.79±5.49小时，表观清除率（CL）为35.91±9.85升。本研究得到的塞来昔布消除速率常数约为0.11±0.05小时⁻¹。