细胞色素P450基因多态性对中国健康受试者单次服用喹硫平药代动力学的影响
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摘要
目的探讨中国健康受试者细胞色素P450 3A4*18B(CYP3A4*18B)和细胞色素P450 3A5*3(CYP3A5*3)基因多态性对喹硫平药代动力学的影响。方法纳入34例中国健康受试者,单次给予喹硫平片25 mg,按照试验方案设计采集血样,检测喹硫平血药浓度,计算药代动力学参数,比较不同基因型对药代动力学参数的影响。结果 G6986A-AA组、G6986A-AG组和G6986A-GG组的Cmax分别为(35. 03±4. 41),(111. 06±33. 46)和(93. 66±41. 25)ng·mL~(-1); AUC_(0-t)分别为(135. 49±27. 65),(316. 97±119. 94)和(288. 22±133. 82) ng·mL~(-1)·h~(-1); AUC_(0-∞)分别为(144. 67±28. 18),(328. 57±122. 08),(300. 83±139. 27) ng·mL~(-1)·h~(-1)。G6986A-AG组、G6986A-GG组的上述指标分别与G6986A-AA组比较,差异均有统计学意义(均P <0. 05)。结论喹硫平在体内的药代动力学参数与CYP3A5*3基因多态性有相关性,根据基因型制定个体化给药方案有助于喹硫平合理使用。
Objective To investigate the effect of CYP3A4*18B and CYP3A5*3 gene polymorphism on the pharmacokinetics of quetiapine in Chinese healthy volunteers. Methods Thirty-four healthy volunteers were enrolled. After a single dose of 25 mg of quetiapine was administered,blood samples were collected according to the protocol,the plasma concentration of quetiapine was measured,and pharmacokinetic parameters were calculated to compare the pharmacokinetic parameters with different genotypes. Results There were statistically significant differences between G6986 A-AA and G6986 A-AG/G6986 A-GG in the Cmax[( 35. 03 ± 4. 41) ng·mL~(-1)/( 111. 06 ± 33. 46) ng·mL~(-1) vs( 93. 66 ± 41. 25) ng·mL~(-1)], the AUC_(0-t)[( 135. 49 ± 27. 65)ng·mL~(-1)·h~(-1)/( 316. 97 ± 119. 94) ng·mL~(-1)· h~(-1) vs( 288. 22 ± 133. 82) ng·mL~(-1)· h~(-1)] and the AUC_(0-∞)[( 144. 67 ±28. 18) ng·mL~(-1)·h~(-1)/( 328. 57 ± 122. 08) ng·mL~(-1)·h~(-1) vs( 300. 83 ± 139. 27) ng·mL~(-1)· h~(-1)]( P < 0. 05).Conclusion The pharmacokinetics of quetiapine in vivo is related to the polymorphism of CYP3 A5* 3 gene. Individualized drug delivery according to genotype can help rational use of quetiapine.
Objective To investigate the effect of CYP3A4*18B and CYP3A5*3 gene polymorphism on the pharmacokinetics of quetiapine in Chinese healthy volunteers. Methods Thirty-four healthy volunteers were enrolled. After a single dose of 25 mg of quetiapine was administered,blood samples were collected according to the protocol,the plasma concentration of quetiapine was measured,and pharmacokinetic parameters were calculated to compare the pharmacokinetic parameters with different genotypes. Results There were statistically significant differences between G6986 A-AA and G6986 A-AG/G6986 A-GG in the Cmax[( 35. 03 ± 4. 41) ng·mL~(-1)/( 111. 06 ± 33. 46) ng·mL~(-1) vs( 93. 66 ± 41. 25) ng·mL~(-1)], the AUC_(0-t)[( 135. 49 ± 27. 65)ng·mL~(-1)·h~(-1)/( 316. 97 ± 119. 94) ng·mL~(-1)· h~(-1) vs( 288. 22 ± 133. 82) ng·mL~(-1)· h~(-1)] and the AUC_(0-∞)[( 144. 67 ±28. 18) ng·mL~(-1)·h~(-1)/( 328. 57 ± 122. 08) ng·mL~(-1)·h~(-1) vs( 300. 83 ± 139. 27) ng·mL~(-1)· h~(-1)]( P < 0. 05).Conclusion The pharmacokinetics of quetiapine in vivo is related to the polymorphism of CYP3 A5* 3 gene. Individualized drug delivery according to genotype can help rational use of quetiapine.
引文
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[5]周建英,刘震天,朱伟锋. COLD-PCR/Sanger法检测非小细胞肺癌患者外周血EGFR和KRAS基因突变的价值[J].南昌大学学报(医学版),2015,55(6):38-41.
[6]刘盈,伍俊妍,丁亮,等.细胞色素P4503A4与P4503A5及多药耐药基因多态性对氨氯地平降压疗效影响研究[J].中国临床药理学杂志,2014,30(11):983-987.
[7]刘晓,胡琨,弓莉,等.细胞色素P4503A4和3A5基因多态性与卡马西平浓度及皮肤药物不良反应的相关性研究[J].中国临床药理学杂志,2016,32(19):1749-1752.
[8] KIM K A,JOO H J,LEE H M,et al. Influence of ABCB1 and CYP3A5 genetic polymorphisms on the pharmacokinetics of quetiapine in healthy volunteers[J]. Pharmacogenet Genomics,2014,24(1):35-42.
[2] BRIMER C,WRIGHTON S A,WATKINS M P,et al. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression[J]. Nat Genet,2001,27(4):383-391.
[3] LEE J S,CHEONG H S,KIM L H,et al. Screening of Genetic Polymorphisms of CYP3A4 and CYP3A5 Genes[J]. Korean J Physiol Pharmacol 2013,17(6):479-484.
[4]戴婕,李芳芳,陈庆强,等.富马酸喹硫平片人体生物等效性研究[J].中国现代应用药学,2013,30(6):614-619.
[5]周建英,刘震天,朱伟锋. COLD-PCR/Sanger法检测非小细胞肺癌患者外周血EGFR和KRAS基因突变的价值[J].南昌大学学报(医学版),2015,55(6):38-41.
[6]刘盈,伍俊妍,丁亮,等.细胞色素P4503A4与P4503A5及多药耐药基因多态性对氨氯地平降压疗效影响研究[J].中国临床药理学杂志,2014,30(11):983-987.
[7]刘晓,胡琨,弓莉,等.细胞色素P4503A4和3A5基因多态性与卡马西平浓度及皮肤药物不良反应的相关性研究[J].中国临床药理学杂志,2016,32(19):1749-1752.
[8] KIM K A,JOO H J,LEE H M,et al. Influence of ABCB1 and CYP3A5 genetic polymorphisms on the pharmacokinetics of quetiapine in healthy volunteers[J]. Pharmacogenet Genomics,2014,24(1):35-42.