CYP2B6~* 6基因多态性对中国健康受试者单次注射丙泊酚的药代动力学和药效学影响

Effect of genetic polymorphism of CYP2B6~* 6 on pharmacokinetics and pharmacodynamics of single dose propofol in Chinese healthy subjects

目的探讨中国健康受试者细胞色素P(CYP)2B6~* 6基因多态性对丙泊酚药代动力学和药效学的影响。方法 20例男性健康受试者单次静脉注射丙泊酚2.0 mg·kg^(-1),用HPLC-MS/MS法测定血药浓度;焦磷酸测序法确定受试者基因型;比较不同基因型受试者的药代动力学和药效学参数。结果 20例受试者中,G516T-GG 14例,G516T-GT/TT 6例;A785G-AA 10例,A785GAG/GG 10例。其中,G516T-GT/TT组和G516T-GG组的意识消失BIS值(BIS-LOC)分别为74.33±7.20和60.43±13.64,差异有统计学意义(P<0.05);A785G-AG/GG组和A785G-AA组t_(1/2β)分别为(0.13±0.06)和(0.41±0.38)h,差异有统计学意义(P<0.05);其他参数C_(max)、t_(max)、AUC_(0-t) AUC_(0-∞)、t_(1/2α)、MRT_(0-∞)、意识消失时间(t-LOC)、BIS-LOC、意识恢复BIS值(BIS-ROC)、达最小BIS值时间(t-BIS_(min))、最小BIS值(BIS_(min))、意识消失持续时间(d-LOC)差异均无统计学意义(均P>0.05)。结论丙泊酚在体内的药代动力学与药效学均与CYP2B6~* 6基因多态性有关,根据基因型制定个体化给药方案有助于丙泊酚合理使用。

Objective To investigate the effects of CYP2 B6＊6 gene polymorphism on the pharmacokinetics and pharmacodynamics of propofol in Chinese healthy subjects. Methods Twenty male healthy subjects were intravenously injected a single dose of 2. 0 mg·kg^-1 propofol. The plasma concentration of propofol was examined by HPLC-MS/MS method. The genotype of the subjects was determined by pyrosequencing.The pharmacokinetics and pharmacodynamic parameters of different genotype were compared. Results Among the 20 subjects,there were 14 cases of G516 T-GG,6 cases of G516 T-GT/TT,10 cases of A785 G-AA and10 cases of A785 G-AG/GG. The bispectral index-loss of conscious（ BIS-LOC） of G516 T-GT/TT group and G516 T-GG group were74. 33 ± 7. 20 and 60. 43 ± 13. 64,the t1/2βof A785 G-AG/GG group and A785 G-AA group were（ 0. 13 ± 0. 06） and（ 0. 41 ± 0. 38） h,with significant difference（ P〈0. 05）. Other parameters like Cmax,tmax,AUC0-t,AUC0-∞,t1/2α,MRT0-∞,t-LOC,BIS-LOC,BIS-ROC,t-BISmin,BISmin, d-LOC all had no statistical significance（ all P〉0. 05）. Conclusion The pharmacokine-tics and pharmacodynamicsof propofol are correlated with the polymorphism of CYP2 B6＊6,individualized dosing regimens based on genotypes contribute to the rational use of propofol.