Influence of CYP2D6*10B genotype on pharmacokinetics of propafenone enantiomers in Chinese subjects
Abstract
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) microg.h.L(-1) for S-enantiomer and (1136+/-345), (1467+/-817), (2277+/-745) microg.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, and the CL of both enantiomers in *10/*10 is only half of that of *1/*10 group or *1/*1 group (P<0.05).
CONCLUSION: CYP2D6*10B alleles induce the declined activity of CYP2D6 and impair the metabolism of propafenone.
Keywords:
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) microg.h.L(-1) for S-enantiomer and (1136+/-345), (1467+/-817), (2277+/-745) microg.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, and the CL of both enantiomers in *10/*10 is only half of that of *1/*10 group or *1/*1 group (P<0.05).
CONCLUSION: CYP2D6*10B alleles induce the declined activity of CYP2D6 and impair the metabolism of propafenone.