Effect of Chronic Administration of Phenobarbital on the Hepatobiliary Transport of Phenol Red: Assessment by Statistical Moment Analysis
Effect of Chronic Administration of Phenobarbital on the Hepatobiliary Transport of Phenol Red: Assessment by Statistical Moment Analysis
复制标题
长期服用苯巴比妥对酚红肝胆转运的影响：统计矩分析评估
作者：
T. Kakutani;K. Endo;E. Nara;Shigenobu Nakazora;M. Hashida
应用一种新的基于统计矩理论的药物定位分析系统(T.Kakutani等，J.Pharmacokin)，研究了酶诱导对苯酚红(PR)在大鼠肝胆中转运的影响。生物制药公司。1985年13：609-631)。根据静脉注射后PR及其代谢物的血药浓度和胆汁浓度的时间曲线，通过将PR分解为肝脏摄取、肝胆转运和肝内代谢等组分子过程，从理论上评价了PR的肝胆转运过程。结果表明，苯巴比妥(PB)诱导的肝酶系统可促进PR的血浆消失，其原因可能是肝脏和肝外清晰度的升高。虽然PB确实引起胆汁流量增加(胆汁排泄)和代谢增加，但这些作用对加速血浆PR的消失几乎没有贡献，因为这表明PR的肝胆排泄受肝内转移过程的速度限制，而PB治疗不影响这一过程。从这项研究的结果来看，这种实验/分析方法似乎有助于从体内数据中获得药物的肝胆转运的详细信息。
The effect of enzyme induction on the hepatobiliary transport of phenol red (PR) in rats was investigated by application of a new analytical system to determine local drug disposition based on statistical moment theory (T. Kakutani et al., J. Pharmacokin. Bio-pharm. 13:609–631, 1985). Employing the moment parameters obtained from the time courses of plasma and biliary concentrations of PR and its metabolite after intravenous injection, the hepatobiliary transport of PR was theoretically assessed by separating it into component subprocesses such as hepatic uptake, hepatobiliary transfer, and intrahepatic metabolism. The results demonstrated that the acceleration of plasma disappearance of PR caused by pretreatment with phenobarbital (PB), known to induce hepatic enzyme systems, could be attributed to elevation of both hepatic and extrahepatic clearances. While PB did cause bile flow elevation (choleresis) and increased metabolism, these effects were shown to make little contribution to accelerated plasma disappearance of PR, since it was shown that the hepatobiliary excretion of PR was rate-limited by the intrahepatic transfer process, which was unaffected by PB treatment. From the results of this study, this experimental/analysis methodology seems to be useful in obtaining detailed information about hepatobiliary transport of the drug from in vivo data.
葡萄糖醛酸化诱导剂和抑制剂对大鼠丙戊酸胆汁排泄和利胆作用的影响。
DOI：
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发表时间：
1982
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
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作者：
Watkins,JB;Klaassen,CD
通讯作者：
Klaassen,CD
影响因子：
21.1
作者：
C. Klaassen;J. Watkins
通讯作者：
C. Klaassen;J. Watkins
孕烯醇酮 16 α-腈在 Gunn、杂合子和 Wistar 大鼠肝脏中诱导 UDP-葡萄糖醛酸基转移酶活性。
DOI：
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发表时间：
1982
期刊：
Drug metabolism and disposition: the biological fate of chemicals
影响因子：
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作者：
Watkins,JB;Klaassen,CD
通讯作者：
Klaassen,CD