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目的:研究CYP2D6表现型在汉族健康受试者普罗帕酮对映体代谢中的作用。方法:选取用右美沙芬进行代谢分型后得到的7名极快代谢者(VEM)和9名中速代谢者(IM)。单剂量口服消旋普罗帕酮400mg,抽取0-15h静脉血。运用反相高压液相色谱法加柱前衍生化,定量分析血浆中普罗帕酮对映体浓度。结果:两种CYP2D6表现型的S-Pro代谢均较R-Pro慢,血浆浓度升高。此外,IM中R-Pro的半衰期比R-Pro大,VEM无此差别。但是,Pro对映体在VEM和IM中的代谢有明显差异。IM组两种对映体的C_(max)和AUC均比VEM组大(P<0.05)。IM组Pro对映体的Cl仅为VEM组的一半[(67±17)vs(133±28)L·h~(-1)for S-Pro,(90±24)vs(200±87)L·h~(-1)for R-Pro,P<0.0]。T_(1/2),T_(max),C_(max),Cl和AUC的S/R比值无显著差异(P>0.05)。结论:CYP2D6表现型决定了普罗帕酮对映体的药动学差异,EM受试者中IM的存在也许与中国人CYP2D6酶活性下降有关。
AIM: To investigate the role of CYP2D6 phenotype in the enantiomeric metabolism of propafenone in healthy Han subjects. Methods: Seven fast metabolizers (VEMs) and nine intermediate metabolizers (IMs) were obtained after metabolic typing with dextromethorphan. Single oral oral racemic propafenone 400mg, 0-15h blood drawn. The enantiomeric concentrations of propafenone in plasma were quantitatively analyzed by RP-HPLC with pre-column derivatization. RESULTS: The S-Pro metabolism of both CYP2D6 phenotypes was slower than that of R-Pro and plasma concentrations increased. In addition, the half-life of R-Pro in IM is greater than that of R-Pro, with no difference in VEM. However, there is a clear difference in the metabolism of Pro enantiomers between VEM and IM. The C_ (max) and AUC of the two enantiomers of IM group were higher than those of VEM group (P <0.05). The Cl of Pro enantiomer of IM group was only half that of VEM group [(67 ± 17) vs (133 ± 28) L · h -1 for S-Pro, (90 ± 24) vs (200 ± 87) L · h ~ (-1) for R-Pro, P <0.0]. The S / R ratio of T_ (1/2), T_ (max), C_ (max), Cl and AUC had no significant difference (P> 0.05). CONCLUSIONS: The CYP2D6 phenotype determines the pharmacokinetic difference of propafenone enantiomers. The presence of IM in EM subjects may be related to the decrease of CYP2D6 activity in Chinese.