Disposition kinetics and metabolism of omeprazole in extensive and poor metabolizers of S-mephenytoin 4'-hydroxylation recruited from an Oriental population.
Disposition kinetics and metabolism of omeprazole in extensive and poor metabolizers of S-mephenytoin 4'-hydroxylation recruited from an Oriental population.
复制标题
从东方人群中招募的 S-美芬妥英 4-羟基化的强代谢者和弱代谢者中奥美拉唑的处置动力学和代谢。
DOI：
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发表时间：
1992
影响因子：
3.5
通讯作者：
T. Ishizaki
中科院分区：
文献类型：
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作者：
D. Sohn;K. Kobayashi;K. Chiba;K. H. Lee;S. Shin;T. Ishizaki
为了探讨奥美拉唑的分布与遗传决定的S-美苯妥因4‘-羟化表型状态的关系，我们从一个朝鲜族人群招募了8个广泛(EM)和8个不良代谢者(PM)，研究了奥美拉唑及其两种主要代谢物(5-羟基奥美拉唑和奥美拉唑砜)在血浆中的动力学变量及其主要代谢物(5-羟基奥美拉唑)在尿中的排泄规律。每个受试者都收到了一份通缉令。剂量为20 mg的奥美拉唑作为肠溶制剂，并在给药后24小时采集血液和尿样。采用高效液相色谱-紫外检测法测定奥美拉唑及其代谢物的含量。奥美拉唑在药-时曲线下的平均面积(AUC)、消除半衰期(T1/2)和表观P.O.PM组的清除量显著大于EMS组(P<0.001)、长于EMS组、低于EMS组(P<0.01)。PM患者5-羟基奥美拉唑的平均峰浓度、AUC及5-羟基奥美拉唑/奥美拉唑的AUC比值均显著低于EM患者(P<0.01~0.01)。PMS患者的平均血药浓度、奥美拉唑酮的AUC及比值均大于EMS患者(P<0.001)，T1/2较EMS患者明显延长(P<0.001)。PMS患者服药后24小时内5-羟基奥美拉唑的平均累积尿量显著低于EMS患者(P<0.001)。此外，尿中对数104‘-羟基苯妥英排泄量与表观氧分压显著相关(P<0.01)。奥美拉唑和奥美拉唑、5-羟基奥美拉唑和奥美拉唑砜的利用度及半衰期。
To explore the relationship between omeprazole disposition and genetically determined S-mephenytoin 4'-hydroxylation phenotype status, we examined the kinetic variables of omeprazole and its two primary metabolites in plasma (5-hydroxyomeprazole and omeprazole sulfone) and the excretion profile of its principal metabolite in urine (5-hydroxyomeprazole) in eight extensive (EMs) and eight poor metabolizers (PMs) recruited from a Korean population. Each subject received a p.o. dose of 20 mg of omeprazole as an enteric-coated formulation, and blood and urine samples were collected up to 24 hr postdose. Omeprazole and its metabolites were measured by high-performance liquid chromatography with ultraviolet detection. The mean omeprazole area under the concentration-time curve (AUC), elimination half-life (T1/2) and apparent p.o. clearance were significantly (P less than .001) greater, longer and lower, respectively, in PMs than in EMs. The mean peak concentration and AUC of 5-hydroxyomeprazole and AUC ratio of 5-hydroxyomeprazole to omeprazole were significantly (P less than .01 to .001) less in PMs than in EMs. The mean peak plasma concentration, AUC of omeprazole sulfone and ratio of omeprazole sulfone to omeprazole were greater (P less than .001) and T1/2 was longer (P less than .001) in PMs than in EMs. The mean cumulative urinary excretion of 5-hydroxyomeprazole up to 24 hr postdose was significantly (P less than .001) less in PMs than in EMs. In addition, the log10 4'-hydroxymephenytoin excreted in urine correlated significantly (P less than .01) with the apparent p.o. clearance of omeprazole and half-lives of omeprazole, 5-hydroxyomeprazole and omeprazole sulfone.(ABSTRACT TRUNCATED AT 250 WORDS)