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1
Rate of elimination of tracer doses of phenytoin at different steady-state serum phenytoin concentrations in epileptic patients.不同稳态血清苯妥英浓度下癫痫患者示踪剂量苯妥英消除率。
Br J Clin Pharmacol. 1974 Apr;1(2):155-61. doi: 10.1111/j.1365-2125.1974.tb00225.x.
2
Inhibition of phenytoin metabolism by sulthiame in epileptic patients.苯妥英钠代谢受磺胺噻唑抑制的癫痫患者。
Br J Clin Pharmacol. 1974 Feb;1(1):59-66. doi: 10.1111/j.1365-2125.1974.tb00207.x.
3
Michaelis-Menten kinetics and the steady-state serum phenytoin/hydroxyphenytoin ratio.
Ther Drug Monit. 1985;7(4):405-10. doi: 10.1097/00007691-198512000-00007.
4
Phenytoin metabolism in subjects with long and short plasma half-lives.血浆半衰期长短不同的受试者中苯妥英的代谢
Ther Drug Monit. 1982;4(3):281-92. doi: 10.1097/00007691-198208000-00006.
5
Phenytoin metabolism in mice.
Drug Metab Dispos. 1982 Mar-Apr;10(2):156-60.
6
Comparative drug elimination in man-diphenylhydantoin and amobarbital.人体内苯妥英钠和异戊巴比妥的药物消除比较
Eur J Clin Pharmacol. 1975 Oct 10;9(1):79-83. doi: 10.1007/BF00613433.
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Studies with stable isotopes I: Changes in phenytoin pharmacokinetics and biotransformation during monotherapy.稳定同位素研究I：苯妥英单药治疗期间药代动力学和生物转化的变化。
J Clin Pharmacol. 1985 Jan-Feb;25(1):43-50. doi: 10.1002/j.1552-4604.1985.tb02799.x.
8
Stereochemistry of aromatic phenytoin hydroxylation in various drug hydroxylation phenotypes in humans.人类不同药物羟化表型中芳香族苯妥英羟化的立体化学
J Pharmacol Exp Ther. 1987 May;241(2):615-22.
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Biliary excretion of diphenylhydantoin in the rat. Time-course studies.
Drug Metab Dispos. 1975 Mar-Apr;3(2):69-73.
10
Stereoselective inhibition of diphenylhydantoin metabolism by p-hydroxyphenyl-phenylhydantoin enantiomers in rats.大鼠体内对羟基苯基苯妥英对映体对苯妥英代谢的立体选择性抑制作用。
Chirality. 1991;3(6):454-9. doi: 10.1002/chir.530030608.

引用本文的文献

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A tracer interaction method for nonlinear pharmacokinetics analysis: application to evaluation of nonlinear elimination.一种用于非线性药代动力学分析的示踪剂相互作用方法：在非线性消除评估中的应用。
J Pharmacokinet Biopharm. 1997 Oct;25(5):569-93. doi: 10.1023/a:1025765330455.
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Dose-dependent pharmacokinetics and cancer chemotherapy.剂量依赖性药代动力学与癌症化疗
Cancer Chemother Pharmacol. 1981;6(1):1-9. doi: 10.1007/BF00253003.
4
Ranitidine versus cimetidine. A comparison of their potential to cause clinically important drug interactions.雷尼替丁与西咪替丁。二者引发具有临床重要性药物相互作用可能性的比较。
Clin Pharmacokinet. 1988 Jul;15(1):44-56. doi: 10.2165/00003088-198815010-00004.
5
[Plasma concentrations after injection or infusion of phenytoin (author's transl)].苯妥英注射或输注后的血浆浓度（作者译）
Klin Wochenschr. 1977 Mar 1;55(5):219-23. doi: 10.1007/BF01487714.
6
The clinical pharmacokinetics of phenytoin.
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7
Clinical pharmacokinetics of phenytoin.苯妥英钠的临床药代动力学
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本文引用的文献

1
Clinical and electroencephalographic correlations with serum levels of diphenylhydanotin.临床及脑电图与血清苯妥英水平的相关性
Arch Neurol. 1960 Jun;2:624-30. doi: 10.1001/archneur.1960.03840120030004.
2
The elimination of salicylic acid in man: serum concentrations and urinary excretion rates.水杨酸在人体中的消除：血清浓度及尿排泄率
Br J Pharmacol Chemother. 1966 Feb;26(2):461-7. doi: 10.1111/j.1476-5381.1966.tb01926.x.
3
Pharmacokinetics of salicylate elimination in man.人体中水杨酸盐消除的药代动力学。
J Pharm Sci. 1965 Jul;54(7):959-67. doi: 10.1002/jps.2600540703.
4
The effect of phenobarbital on plasma diphenylhydantoin level and metabolism in man and in rat liver microsomes.苯巴比妥对人体及大鼠肝微粒体中血浆苯妥英水平和代谢的影响。
Neurology. 1969 Jun;19(6):611-6. doi: 10.1212/wnl.19.6.611.
5
Studies on the metabolism of diphenylhydantoin in mice.
J Pharmacol Exp Ther. 1969 May;167(1):77-90.
6
Study of dose-dependent metabolism of 5,5-diphenyl-hydantoin in the rat using new methodology for isolation and quantitation of metabolites in vivo and in vitro.使用体内和体外代谢物分离与定量新方法对大鼠体内5,5-二苯基乙内酰脲的剂量依赖性代谢进行研究。
J Pharmacol Exp Ther. 1971 Sep;178(3):567-79.
7
Diphenylhydantoin intoxication attendant to slow inactivation of isoniazid.异烟肼缓慢失活导致的苯妥英中毒
Neurology. 1970 Jul;20(7):687-93. doi: 10.1212/wnl.20.7.687.
8
Supervision of epileptic patients taking phenytoin.对服用苯妥英钠的癫痫患者的监护
Br Med J. 1970 Jan 17;1(5689):147-9. doi: 10.1136/bmj.1.5689.147.
9
The rate of decline of diphenylhydantoin in human plasma.人体血浆中苯妥英的下降速率。
Clin Pharmacol Ther. 1970 Jan-Feb;11(1):121-34. doi: 10.1002/cpt1970111121.
10
Influence of ethylphenacemide on serum levels of other anti-epileptic drugs.
Epilepsia. 1970 Jun;11(2):207-15. doi: 10.1111/j.1528-1157.1970.tb03882.x.

不同稳态血清苯妥英浓度下癫痫患者示踪剂量苯妥英消除率。

Rate of elimination of tracer doses of phenytoin at different steady-state serum phenytoin concentrations in epileptic patients.

机构信息

Department of Clinical Pharmacology, St Bartholomew's Hospital, London.

出版信息

Br J Clin Pharmacol. 1974 Apr;1(2):155-61. doi: 10.1111/j.1365-2125.1974.tb00225.x.

DOI:10.1111/j.1365-2125.1974.tb00225.x
PMID:22454903
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1402453/
Abstract

1 Serum phenytoin concentration, the serum half-life of a tracer dose of carbon-labelled phenytoin, and the ratio of the major metabolite of phenytoin to unchanged drug in urine (p-HPPH: DPH ratio) were measured in epileptic patients on chronic anticonvulsant therapy. 2 A significant correlation was found between serum phenytoin concentration and half-life, the slope of the regression line being dose dependent. 3 A significant negative correlation was found between serum phenytoin concentration and p-HPPH: DPH ratio. 4 Increasing the daily dose of phenytoin lead to a lengthening of the half-life and a reduction in the p-HPPH: DPH ratio. The reverse occurred on lowering the dose. 5 These changes indicate that phenytoin hydroxylation is saturable. 6 Difficulty in achieving a stable serum phenytoin concentration within the therapeutic range may result.

摘要

  1. 在接受慢性抗惊厥治疗的癫痫患者中，测定了血清苯妥英钠浓度、放射性标记苯妥英的血清半衰期、以及尿中苯妥英主要代谢物与未改变药物的比值（p-HPPH:DPH 比值）。

  2. 发现血清苯妥英钠浓度与半衰期之间存在显著相关性，回归线斜率呈剂量依赖性。

  3. 发现血清苯妥英钠浓度与 p-HPPH:DPH 比值之间存在显著负相关。

  4. 增加苯妥英钠的日剂量会导致半衰期延长和 p-HPPH:DPH 比值降低。降低剂量则反之。

  5. 这些变化表明苯妥英羟基化是饱和的。

  6. 可能导致难以在治疗范围内达到稳定的血清苯妥英浓度。