TY - JOUR
T1 - Effects of the CYP2C9*1/*13 genotype on the pharmacokinetics of lornoxicam
AU - Choi, Chang Ik
AU - Kim, Mi Jeong
AU - Jang, Choon Gon
AU - Park, Young Seo
AU - Bae, Jung Woo
AU - Lee, Seok Yong
PY - 2011/12
Y1 - 2011/12
N2 - 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 8mg 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 24hr 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.
AB - 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 8mg 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 24hr 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.
UR - https://www.scopus.com/pages/publications/81255162560
U2 - 10.1111/j.1742-7843.2011.00751.x
DO - 10.1111/j.1742-7843.2011.00751.x
M3 - Article
C2 - 21726410
AN - SCOPUS:81255162560
SN - 1742-7835
VL - 109
SP - 476
EP - 480
JO - Basic and Clinical Pharmacology and Toxicology
JF - Basic and Clinical Pharmacology and Toxicology
IS - 6
ER -