CYP2D6 phenotype determines pharmacokinetic variability of propafenone enantiomers in 16 HAN Chinese subjects

ATM: To determine the role of the CYP2D6 phenotype in the metabolism of pro pafenone (Pro) enantiomers in 16 HAN Chinese subjects. METHODS: Seven very extensive metabolizers (VEM) and nine intermediate metabolizers (IM) were e nrolled from a Chinese population whose phenotype had been previously asses sed with a dextromethorphan metabolic phenotyping. The blood samples (0 - 1 5 h) were taken after oral administration of a single dose (400 mg) of rac- Pro hydrochloride. Enantiomeric concentrations of propafenone in plasma wer e measured by a reverse-phase HPLC with precolumn derivatization. RESULTS: S-Pro was less metabolized and had higher plasma concentrations than R-Pro in both CYP2D6 phenotypes. Besides, the T-1/2 of R-Pro was longer than that of S-Pro in IM, but not in VEM. However, there were significant difference s in the metabolism of Pro enantiomers between VEM and IM. The C-max and AU C of both isomers in the IM group were higher than those in the VEM group ( P <0.01). The CZ of Pro enantiomers in IM group was only about half of that in VEM group [(67 +/- 17) vs (133 +/- 28) L . h(-1) for S-Pro, (90+/-24) v s (200+/-87) L . h(-1) for R-Pro, P<0.01]. The S/R ratios of T-1/2, T-max, C-max CI, and AUC were not significantly different (P > 0.05). CONCLUSION: CYP2D6 phenotype determines the pharmacokinetic variability of propafenone enantiomers and existence of IM may be relevant to diminished capacity of C YP2D6 enzyme in Chinese subjects.