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髋关节手术后患者血浆、CSF 和伤口组织中依托考昔的吸收和分布-一项初步研究。

Absorption and distribution of etoricoxib in plasma, CSF, and wound tissue in patients following hip surgery--a pilot study.

机构信息

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Krankenhausstr. 9, 91054 Erlangen, Germany.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2010 Feb;381(2):127-36. doi: 10.1007/s00210-009-0482-0. Epub 2010 Jan 6.

Abstract

The perioperative administration of selective cyclooxygenase-2 (COX-2)-inhibitors to avoid postoperative pain is an attractive option: they show favorable gastro-intestinal tolerability, lack inhibition of blood coagulation, and carry a low risk of asthmatic attacks. The purpose of this study was to determine the cerebrospinal fluid (CSF), plasma, and tissue pharmacokinetics of orally administered etoricoxib and to compare it with effect data, i.e., COX-2-inhibition in patients after hip surgery. The study was performed in a blinded, randomized, parallel group design. A total of 12 adult patients were included who received 120 mg etoricoxib (n = 8) or placebo (n = 4) on day 1 post-surgery. Samples from plasma, CSF, and tissue exudates were collected over a period of 24 h post-dosing and analyzed for etoricoxib and prostaglandin E(2) (PGE(2)) using liquid chromatography-tandem mass spectrometry and immuno-assay techniques. CSF area under the curve (AUC) [AUCs((O-24h))] for etoricoxib amounted to about 5% of the total AUC in plasma (range: 2-7%). Individual CSF lag times with respect to (50%) peak plasma concentration were </=2 h in all but one case (median: 1 h). PGE(2) production in tissue was significantly blocked by the COX-2 inhibitor starting with the appearance of etoricoxib in tissue and lasting for the whole observation period of 24 h (P < 0.01). In conclusion, etoricoxib reaches the CSF and site of surgery at effective concentrations and reduces PGE(2) production at the presumed site of action.

摘要

围手术期应用选择性环氧化酶-2(COX-2)抑制剂来预防术后疼痛是一种很有吸引力的选择:它们具有良好的胃肠道耐受性,不抑制凝血,并且哮喘发作的风险低。本研究的目的是确定口服依托考昔的脑脊液(CSF)、血浆和组织药代动力学,并将其与效应数据(即髋关节手术后患者的 COX-2 抑制)进行比较。该研究采用盲法、随机、平行组设计进行。共纳入 12 例成年患者,术后第 1 天分别给予依托考昔 120mg(n=8)或安慰剂(n=4)。在给药后 24 小时内采集血浆、CSF 和组织渗出液样本,并采用液相色谱-串联质谱法和免疫测定技术分析依托考昔和前列腺素 E2(PGE2)。依托考昔的 CSF 曲线下面积(AUC)[AUCs(O-24h)]约为血浆总 AUC 的 5%(范围:2-7%)。除 1 例外,所有患者的 CSF 滞后时间相对于(50%)血浆峰浓度均为</=2 小时(中位数:1 小时)。组织中 COX-2 抑制剂的 PGE2 生成从组织中出现依托考昔时开始并持续整个 24 小时的观察期(P<0.01),显著被阻断。总之,依托考昔可到达 CSF 和手术部位,并在假定作用部位降低 PGE2 的产生,达到有效浓度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35e3/2807935/2707add7ff76/210_2009_482_Fig1_HTML.jpg

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