Influence of CYP2D610B genotype on pharmacokinetics of propafenone enantiomers in Chinese subjects

• 出 处: Acta Pharmacologica Sinica
• 发表日期: 2003年12期
• 关键词: genotype allele administration mutant Genotype Pharmacol substitution population

AIM: To study the relationship between genotype of CYP2D6* 10B and pharmacokinetics of propafenone enantiomers. METHODS: Genotype of 17 healthy Chinese HAN subjects was determined by an allele specific amplification method. The blood samples (0-15 h) of the subjects were taken after oral administration of a single dose (400 mg) of propafenone hydrochloride. Concentrations of propafenone enantiomers in plasma were measured by a reverse-phase HPLC with precolumn derivatization. RESULTS: Seventeen subjects characterized for CYP2D6* 10B genotype included (*1/*1) (n=4), (*1/*10) (n=5) and (*10/*10) (n=8). The metabolic ratios (lg MR) of the three genotypes were-2.68±0.23, -2.2±0.7, and -1.1±0.5, respectively. The AUC of the three groups were (1534±334), (1891±793), (3171±1075) μg·h·L~(-1) for S-enantiomer and (1136±345), (1467±817), (2277±745) μg·h·L~(-1) for R-enantiomer, respectively. The AUC of propafenone enantiomers in *10/*10 is about 1.5-2 times of that of *1/*10 group or *1/*1 group, a

AIM: To study the relationship between genotype of CYP2D6 * 10B and pharmacokinetics of propafenone enantiomers. METHODS: Genotype of 17 healthy Chinese HAN subjects was determined by an allele specific amplification method. The blood samples (0-15 h) of the subjects were After oral administration of a single dose (400 mg) of propafenone hydrochloride. Concentrations of propafenone enantiomers in plasma were measured by a reverse-phase HPLC with precolumn derivatization. RESULTS: Seventeen constitution characterized for CYP2D6 * 10B genotype included (* 1 / * 1 (n = 4), (* 1 / * 10) (n = 5) and (* 10 / * 10) (n = 8). The metabolic ratios (lg MR) of the three genotypes were-2.68 ± 0.23, -2.2 ± 0.7, and -1.1 ± 0.5, respectively. The AUC of the three groups were (1534 ± 334), (1891 ± 793), (3171 ± 1075) μg · h · L -1 for S- enantiomer and (1136 ± 345), (1467 ± 817), (2277 ± 745) μg · h · L -1 for R-enantiomer, respectively. The AUC of propafenone enantiomers in * 10 / * 10 is about 1.5 -2 times of that of * 1 / * 10 group or * 1 / * 1 group, a