Effect of cytochrome P450 2D6*10 polymorphism on the pharmacokinetics of oral nebivolol after single and multiple doses
10.13699/j.cnki.1001-6821.2015.21.009
- VernacularTitle:细胞色素 P4502 D6*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
- Author:
Ning-Fang CAI
1
;
Bi-Feng LI
;
Xiao-Hong HUANG
;
Ke-Zhen XU
;
Meng-Yun CAI
;
Hui-Ping FENG
;
Li-Hua HE
;
Min YU
;
Xin GUO
;
Ze-Neng CHENG
Author Information
1. 漳州市医院 药学部
- Keywords:
nebivolol;
cytochrome P450 2D6*10;
polymorphism;
pharmacokinetic
- From:
The Chinese Journal of Clinical Pharmacology
2015;(21):2114-2117
- CountryChina
- Language:Chinese
-
Abstract:
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.
