School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
Basic Clin Pharmacol Toxicol. 2011 Dec;109(6):476-80. doi: 10.1111/j.1742-7843.2011.00751.x. Epub 2011 Aug 8.
Lornoxicam is extensively metabolized by CYP2C9, and a CYP2C913 is one of the principal variant alleles in East Asian populations. The aim of this study was to evaluate the effects of CYP2C91/13 on the pharmacokinetic parameters of lornoxicam in healthy individuals. A single oral dose of 8 mg lornoxicam was given to 22 Korean volunteers with different CYP2C9 genotypes (8, 8 and 6 carriers of CYP2C91/*1, *1/*3 and *1/13 genotypes, respectively). Lornoxicam and 5'-hydroxylornoxicam levels were analysed using HPLC-UV in plasma samples collected up to 24 hr after taking the drug. In individuals with CYP2C91/13, lornoxicam had a higher C(max) (p < 0.001), a longer half-life (p < 0.001), a lower oral clearance (p < 0.001) and a higher area under the plasma concentration-time curve from zero to infinity (AUC(inf) ) than in CYP2C91/1 individuals (p < 0.001). The C(max) and AUC(inf) of 5'-hydroxylornoxicam were lower in CYP2C91/13 individuals than in CYP2C91/1 individuals, but the half-life of 5'-hydroxylornoxicam did not differ between the two groups. The half-life, oral clearance and AUC(inf) of lornoxicam were similar in individuals with CYP2C91/13 and those with CYP2C91/3. The C(max) , half-life and AUC(inf) of 5'-hydroxylornoxicam were also similar in both groups, although C(max) was higher in CYP2C91/13 individuals (p < 0.01). A CYP2C91/13 genotype markedly reduced the conversion of lornoxicam to 5'-hydroxylornoxicam, to a similar extent as that observed with the CYP2C91/*3 genotype.
氯诺昔康主要通过 CYP2C9 代谢，而 CYP2C913 是东亚人群中主要的变异等位基因之一。本研究旨在评估 CYP2C91/13 对健康个体中氯诺昔康药代动力学参数的影响。22 名韩国志愿者分别给予 8mg 氯诺昔康单剂量，其 CYP2C9 基因型分别为 CYP2C91/*1（8 名）、*1/3（8 名）和1/13（6 名）。用药后 24 小时内采集血样，采用 HPLC-UV 法测定血浆中氯诺昔康和 5'-羟基氯诺昔康浓度。在 CYP2C91/13 个体中，C(max)（p < 0.001）、半衰期（p < 0.001）、口服清除率（p < 0.001）和 0 至无穷时血浆浓度-时间曲线下面积（AUC(inf)）（p < 0.001）均高于 CYP2C91/1 个体。与 CYP2C91/1 个体相比，CYP2C91/13 个体 5'-羟基氯诺昔康的 C(max)和 AUC(inf)较低，但两组间 5'-羟基氯诺昔康半衰期无差异。CYP2C91/13 个体和 CYP2C91/3 个体的氯诺昔康半衰期、口服清除率和 AUC(inf)相似。两组 5'-羟基氯诺昔康的 C(max)、半衰期和 AUC(inf)也相似，尽管 CYP2C91/13 个体的 C(max)较高（p < 0.01）。CYP2C91/13 基因型显著降低了氯诺昔康转化为 5'-羟基氯诺昔康的程度，与 CYP2C91/*3 基因型相似。
