title: Effects of the CYP2C9*1/*13 genotype on the pharmacokinetics of lornoxicam.
abstract: 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.
authors: School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.  
authors: Chang-Ik
authors: CI
authors: Choi
authors: Mi-Jeong
authors: MJ
authors: Kim
authors: Choon-Gon
authors: CG
authors: Jang
authors: Young-Seo
authors: YS
authors: Park
authors: Jung-Woo
authors: JW
authors: Bae
authors: Seok-Yong
authors: SY
authors: Lee
mesh_terms: D000328:Adult; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016861:Cyclooxygenase Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D065729:Cytochrome P-450 CYP2C9; D004247:DNA / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006574:Heterocyclic Compounds, 2-Ring / Q000097:blood; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D010894:Piroxicam / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D011110:Polymorphism, Genetic; D011725:Pyridines / Q000097:blood; D056910:Republic of Korea; D055815:Young Adult
chemical_list: C509590:5'-hydroxylornoxicam; D016861:Cyclooxygenase Inhibitors; D006574:Heterocyclic Compounds, 2-Ring; D011725:Pyridines; D010894:Piroxicam; D004247:DNA; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C059451:lornoxicam