Influence of CYP2C8*2 on the pharmacokinetics of pioglitazone in healthy African-American volunteers.
Influence of CYP2C8*2 on the pharmacokinetics of pioglitazone in healthy African-American volunteers.
复制标题
CYP2C8*2对健康非裔美国志愿者中吡格列酮药代动力学的影响。
DOI：
10.1002/phar.1292
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发表时间：
2013-09
期刊：
影响因子：
4.1
通讯作者：
Sidhom, Maha S.
中科院分区：
文献类型：
--
作者：
Aquilante, Christina L.;Wempe, Michael F.;Spencer, Samantha H.;Kosmiski, Lisa A.;Predhomme, Julie A.;Sidhom, Maha S.
To determine the influence of the CYP2C8*2 polymorphism on pioglitazone pharmacokinetics in healthy African American volunteers. Prospective, open-label, single-dose pharmacokinetic study. University of Colorado Hospital Clinical and Translational Research Center. Healthy African-American volunteers between 21 to 60 years of age were enrolled in the study based on CYP2C8 genotype: CYP2C8*1/*1 (n=9), CYP2C8*1/*2 (n=7), and CYP2C8*2/*2 (n=1). Participants received a single 15 mg dose of pioglitazone in the fasted state, followed by a 48-hour pharmacokinetic study. Plasma concentrations of pioglitazone and its M-III (keto) and M-IV (hydroxy) metabolites were compared between participants with the CYP2C8*1/*1 genotype and CYP2C8*2 carriers. Pioglitazone AUC0-∞ and t1/2 did not differ significantly between CYP2C8*1/*1 and CYP2C8*2 carriers (AUC0-∞,7331 ± 2846 versus 10431 ± 5090 ng*h/ml, p=0.15; t1/2, 7.4 ± 2.7 versus 10.5 ± 4.0 h, p=0.07). M-III and M-IV AUC0-48 also did not differ significantly between genotype groups. However, the M-III/pioglitazone AUC0-48 ratio was significantly lower in CYP2C8*2 carriers than CYP2C8*1 homozygotes (0.70 ± 0.15 versus 1.2 ± 0.37, p=0.006). Similarly, CYP2C8*2 carriers had a significantly lower M-III/M-IV AUC0-48 ratio than participants with the CYP2C8*1/*1 genotype (0.82 ± 0.26 versus 1.22 ± 0.26, p=0.006). These data suggest that CYP2C8*2 influences pioglitazone pharmacokinetics in vivo, particularly the AUC0-48 ratio of M-III to parent drug, and the AUC0-48 ratio of M-III to M-IV. Additional, larger studies are needed to further investigate the impact of CYP2C8*2 on the pharmacokinetics of CYP2C8 substrates in individuals of African descent.
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影响因子：
2.1
作者：
Gil JP;Gil Berglund E
通讯作者：
Gil Berglund E
影响因子：
4.1
作者：
Andrisin, TE;Humma, LM;Johnson, JA
通讯作者：
Johnson, JA
DOI：
10.1097/00008571-200110000-00006
发表时间：
2001-10-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Dai, D;Zeldin, DC;Goldstein, JA
通讯作者：
Goldstein, JA
影响因子：
3.4
作者：
Aquilante, Christina L.;Kosmiski, Lisa A.;Sidhom, Maha S.
通讯作者：
Sidhom, Maha S.
影响因子：
3.4
作者：
Jaakkola, T;Backman, JT;Neuvonen, PJ
通讯作者：
Neuvonen, PJ