CAJ | 학술논문

目的：评价细胞色素P4502D6*10（ CYP2D6*10）基因多态性对单次及多次口服奈必洛尔药代动力学的影响。方法根据CYP2D6*10基因型选择入选15名中国健康受试者，其中CYP2D6*1携带者8名，CYP2D6*10／*10基因型7名。所有受试者单次口服奈必洛尔5 mg和多次口服奈必洛尔5 mg? d－1，qd，连续7 d。用LC－MS／MS法测定奈必洛尔血药浓度，用WinNonlin软件计算主要的药代动力学参数。结果单次口服奈必洛尔后 CYP2D6*1携带者和CYP2D6*10／*10基因型个体中奈必洛尔的主要药代动力学参数：t1／2分别为（9．88±5．47），（12．29±6．19） h； AUCinf分别为（7．26±5．88），（8．56±5．20）μg? L－1? h；Cmax分别为（1．11±0．53），（1．42±0．75）μg? L－1。多次口服奈必洛尔后CYP2D6*1携带者和CYP2D6*10／*10基因型个体中奈必洛尔的主要药代动力学参数：t1／2分别为（8．56±2．38），（7．67±4．75） h； AUCinf分别为（10．62±5．62），（12．74±7．40）μg? L－1? h；Cmax分别为（2．05±0．83），（2．02±0．75）μg? L－1。奈必洛尔主要药代动力学参数在不同基因型组间比较差异无统计学意义（ P＞0．05）。多次给药的清除率在不同基因型中均显著低于单次给药（P＜0．05）。结论 CYP2D6*10基因多态性对单次及多次口服奈必洛尔药代动力学无显著影响。多次给药后奈必洛尔体内消除减慢，且不受CYP2D6*10基因多态性影响。
목적：평개세포색소P4502D6*10（ CYP2D6*10）기인다태성대단차급다차구복내필락이약대동역학적영향。방법근거CYP2D6*10기인형선택입선15명중국건강수시자，기중CYP2D6*1휴대자8명，CYP2D6*10／*10기인형7명。소유수시자단차구복내필락이5 mg화다차구복내필락이5 mg? d－1，qd，련속7 d。용LC－MS／MS법측정내필락이혈약농도，용WinNonlin연건계산주요적약대동역학삼수。결과단차구복내필락이후 CYP2D6*1휴대자화CYP2D6*10／*10기인형개체중내필락이적주요약대동역학삼수：t1／2분별위（9．88±5．47），（12．29±6．19） h； AUCinf분별위（7．26±5．88），（8．56±5．20）μg? L－1? h；Cmax분별위（1．11±0．53），（1．42±0．75）μg? L－1。다차구복내필락이후CYP2D6*1휴대자화CYP2D6*10／*10기인형개체중내필락이적주요약대동역학삼수：t1／2분별위（8．56±2．38），（7．67±4．75） h； AUCinf분별위（10．62±5．62），（12．74±7．40）μg? L－1? h；Cmax분별위（2．05±0．83），（2．02±0．75）μg? L－1。내필락이주요약대동역학삼수재불동기인형조간비교차이무통계학의의（ P＞0．05）。다차급약적청제솔재불동기인형중균현저저우단차급약（P＜0．05）。결론 CYP2D6*10기인다태성대단차급다차구복내필락이약대동역학무현저영향。다차급약후내필락이체내소제감만，차불수CYP2D6*10기인다태성영향。
Objective To evaluate the effect of cytochrome P450 2 D6*10 ( CYP2 D6*10 ) polymorphism on the pharmacokinetics of oral nebivolol after single and multiple doses. Methods Fifteen healthy volunteers which were selected according to their CYP2D6*10 genotype, consisted of 8 of CYP2D6*1 carriers and 7 of CYP2D6*10/*10 geno-types.All subjects received a single dose of 5 mg and multiple doses (5 mg? d-1 , qd, for 7 days) .Nebivolol in plasma were measured by LC-MS/MS.The main pharmacokinetic parameters were calculated by WinNonlin program.Results The main pharmacokinetic parameters of nebivolol in plasma between CYP2D6*1 carriers and CYP2D6*10/*10 genotypes after a single dose were as follows: t1/2 were (9.88 ±5.47), ( 12.29 ±6.19 ) h, AUCinf were ( 7.26 ±5.88 ), (8.56 ±5.20)μg? L-1? h, Cmax were (1.11 ±0.53), (1.42 ±0.75)μg? L-1 , respectively.The main pharmacokinetic parameters of nebivolol in plasma between CYP2D6*1 carriers and CYP2D6*10/*10 genotypes after multiple doses were as follows:t1/2 were (8.56 ±2.38), (7.67 ±4.75) h, AUCinf were (10.62 ±5.62), (12.74 ±7.40)μg? L-1? h, Cmax were (2.05 ±0.83), (2.02 ±0.75)μg? L-1, respectively.No significant differences in the pharmacokinetic parameters of nebivolol were found between CYP2D6*1 carriers and CYP2D6*10/*10 genotypes.The clearance of the multiple doses was significantly lower compared with that of single dose in the different genotyped groups.Conclusion CYP2D6*10 polymorphism has no significant effect on the pharmacokinetics of oral nebivolol after single and multiple doses.The elimination of nebivolol decreases after the multiple doses, which is not affected by CYP2D6*10 polymorphism.