Inhibitory effect of troleandomycin on the metabolism of omeprazole is CYP2C19 genotype-dependent
Inhibitory effect of troleandomycin on the metabolism of omeprazole is CYP2C19 genotype-dependent
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DOI：
10.1080/0049825021000023996
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发表时间：
2003-02-01
期刊：
影响因子：
1.8
通讯作者：
Zhou, HH
中科院分区：
文献类型：
--
作者：
He, N;Huang, SL;Zhou, HH
1. 18名健康CYP2C19基因型男性受试者在OP给药前接受20 mg奥美拉唑（OP）单独口服或接受醋竹桃霉素（TAO）500 mg每日给药2天。采集血样，采用反相高效液相色谱法测定血浆中OP 5-羟基奥美拉唑（5-OH-OP）和OP砜的浓度. TAO组的OP在弱代谢者（PM）中的平均C（max）、AUC和CL均大于无TAO组。与未使用TAO相比，使用TAO时PM中5-OH-OP的C（max）和AUC显著（p <0.05）降低。除AUC外，TAO杂合子快代谢型（EM）与未TAO杂合子快代谢型（EM）之间的5-OH-OP差异与PM中观察到的差异相似。而在纯合子EM中，TAO的作用无统计学差异. TAO对OP及其两种主要代谢产物代谢的影响在CYP2C19的不同基因型组中不同。CYP3A4不仅在OP砜的形成中起主导作用，而且还参与OP的5-羟基化，CYP2C19和CYP3A都参与5-OH-OP和OP砜的进一步消除。
1. Eighteen healthy CYP2C19 gencityped male subjects were administered a 20-mg oral dose of omeprazole (OP) alone or received troleandomycin (TAO) 500 mg daily for 2 days before the dose of OP was administered. Blood samples were obtained and OP 5-hydroxyomeprazole (5-OH-OP) and OP sulfone in plasma were determined by reversed-phase HPLC.2. The mean C(max), AUC and CL for OP in poor metabolizers (PMs) were greater with TAO than without TAO. The C(max) and AUC of 5-OH-OP in PMs were significantly (p < 0.05) less with TAO than without TAO. The differences in 5-OH-OP between heterozygous extensive metabolizers (EMs) with TAO versus without TAO were similar to those observed in PMs, except for the AUC. However, in homozygous EMs, there were no statistical differences for the effect of TAO.3. The effect of TAO on the metabolism of OP and its two principal metabolites differs in different genotype groups of CYP2C19. CYP3A4 not only plays a dominant role in the formation of OP sulfone, but also it contributes to the 5-hydroxylation of OP. Both CYP2C19 and CYP3A contribute to the further elimination of 5-OH-OP and OP sulfone.