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Effects of the CYP2C9*1/*13 genotype on the pharmacokinetics of lornoxicam.

Lornoxicam is extensively metabolized by CYP2C9, and a CYP2C9*13 is one of the principal variant alleles in East Asian populations. The aim of this study was to evaluate the effects of CYP2C9*1/*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 CYP2C9*1/*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 CYP2C9*1/*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 CYP2C9*1/*1 individuals (p < 0.001). The C(max) and AUC(inf) of 5'-hydroxylornoxicam were lower in CYP2C9*1/*13 individuals than in CYP2C9*1/*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 CYP2C9*1/*13 and those with CYP2C9*1/*3. The C(max) , half-life and AUC(inf) of 5'-hydroxylornoxicam were also similar in both groups, although C(max) was higher in CYP2C9*1/*13 individuals (p < 0.01). A CYP2C9*1/*13 genotype markedly reduced the conversion of lornoxicam to 5'-hydroxylornoxicam, to a similar extent as that observed with the CYP2C9*1/*3 genotype.