Activities of cytochrome P450 1A2, N-acetyltransferase 2, xanthine oxidase, and cytochrome P450 2D6 are unaltered in children with cystic fibrosis
Activities of cytochrome P450 1A2, N-acetyltransferase 2, xanthine oxidase, and cytochrome P450 2D6 are unaltered in children with cystic fibrosis
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DOI：
10.1016/j.clpt.2003.10.005
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发表时间：
2004-03-01
影响因子：
6.7
通讯作者：
Kearns, GL
中科院分区：
文献类型：
--
作者：
Kennedy, MJ;Scripture, CD;Kearns, GL
采用标准咖啡因和右美沙芬表型方法，对12例3~8岁轻度囊性纤维化(CF)患儿和12例年龄匹配的健康儿童肝组织细胞色素P450(CYP)1A2、N-乙酰转移酶2(NAT-2)、黄嘌呤氧化酶(XO)和细胞色素P2D6的活性进行了检测。受试者被给予4盎司可口可乐(约35毫克咖啡因)(佐治亚州亚特兰大可口可乐公司)和单剂量0.5毫克/公斤的右美沙芬。在给予生物标志物后8小时收集尿液，并使用先前验证的咖啡因和右美沙芬摩尔比来评估酶活性。同时对12例CF患者中的10例和12例正常对照中的11例进行了CYP2D6基因分型。在所评估的任何酶系统中，尿摩尔比率没有显著差异。这些数据表明，Cf不改变CY-P1A2、NAT-2、XO和CYP2D6的活性。在这一患者群体中，药物的生物转化改变可能是酶和异构体特有的，因此只有选定的作为酶底物的化合物才明显，而不是CYP1A2、NAT-2、XO和CYP2D6。
The activities of hepatic cytochrome P450 (CYP) 1A2, N-acetyltransferase 2 (NAT-2), xanthine oxidase (XO), and CYP2D6 were evaluated in 12 young children (aged 3-8 years) with mild cystic fibrosis (CF) and 12 age-matched healthy control subjects by use of standard caffeine and dextromethorphan phenotyping methods. Subjects were given 4 oz of Coca-Cola (approximately 35 mg caffeine) (The Coca-Cola Company, Atlanta, Ga) and a single 0.5-mg/kg dose of dextromethorphan. Urine was collected for 8 hours after biomarker administration, and enzyme activity was assessed by use of previously validated caffeine and dextromethorphan molar ratios. CYP2D6 genotyping was also performed in 10 of 12 subjects with CF and 11 of 12 control subjects. There were no significant differences in the urinary molar ratios for any of the enzyme systems evaluated. These data suggest that CF does not alter the activities of CY-P1A2, NAT-2, XO, and CYP2D6. Altered biotransformation of drugs in this patient population is likely enzyme- and isoform-specific and thus is apparent for only selected compounds that are substrates for enzymes other than CYP1A2, NAT-2, XO, and CYP2D6.