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异戊巴比妥代谢物的独特模式。

Distinctive patterns of amobarbital metabolites.

作者信息

Kalow W, Tang B K, Kadar D, Inaba T

出版信息

Clin Pharmacol Ther. 1978 Nov;24(5):576-82. doi: 10.1002/cpt1978245576.

DOI:10.1002/cpt1978245576
PMID:699482
Abstract

This paper establishes that the relative proportion of amobarbital metabolites in urine is highly variable from person to person and that observations of plasma half-life give no indication of this variability, but it shows that a valid estimate of a given person's metabolite pattern can be obtained by studying a single urine specimen in the postdistributive phase. The two metabolites which were measured in urine accounted on the average of 9 subjects for 80% +/- 3% of the dose with a range from 66% to 94%. The two metabolites were the well known 3'-hydroxyamobarbital (COH) as a product of side chain hydroxylation and N-beta-D-glucopyranosyl amobarbital (N-glu), a glucose conjugate which at some earlier time had been mistaken for an N-hydroxylation product. Among 129 volunteer subjects, the metabolite ratio N-glu/COH showed a median value of about 0.5 with a range from 0 to 2.8. A virtual absence of N-glu was observed in one of the 129 subjects and confirmed by a second administration of amobarbital 3 mo later. Of the 14 subjects with predominant N-glu excretion 4 were of Chinese origin, while there were 6 Chinese among the 115 other subjects (p less than 0.02).

摘要

本文证实,尿液中异戊巴比妥代谢物的相对比例因人而异,血浆半衰期的观察结果无法显示这种变异性,但研究表明,在分布后阶段分析单个尿液样本,就能有效估计特定个体的代谢物模式。在9名受试者的尿液中检测到的两种代谢物,平均占给药剂量的80%±3%,范围为66%至94%。这两种代谢物分别是众所周知的3'-羟基异戊巴比妥(COH),它是侧链羟基化的产物;以及N-β-D-吡喃葡萄糖基异戊巴比妥(N-葡糖),一种葡萄糖结合物,在早些时候曾被误认为是N-羟基化产物。在129名志愿者中,代谢物N-葡糖/COH的比例中位数约为0.5,范围从0至2.8。在129名受试者中有1名几乎没有N-葡糖,3个月后再次给予异戊巴比妥得到了证实。在14名以N-葡糖排泄为主的受试者中,有4名是华裔,而在其他115名受试者中有6名华裔(p<0.02)。

相似文献

1
Distinctive patterns of amobarbital metabolites.异戊巴比妥代谢物的独特模式。
Clin Pharmacol Ther. 1978 Nov;24(5):576-82. doi: 10.1002/cpt1978245576.
2
A case of deficiency of N-hydroxylation of amobarbital.一例异戊巴比妥N-羟化缺乏症。
Clin Pharmacol Ther. 1977 May;21(5):530-5. doi: 10.1002/cpt1977215530.
3
N-hydroxyamobarbital: the second major metabolite of amobarbital in man.N-羟基异戊巴比妥:人体内异戊巴比妥的第二种主要代谢产物。
Drug Metab Dispos. 1975 Nov-Dec;3(6):479-86.
4
A method for studying drug metabolism in populations: racial differences in amobarbital metabolism.一种研究人群中药物代谢的方法:异戊巴比妥代谢的种族差异
Clin Pharmacol Ther. 1979 Dec;26(6):766-76. doi: 10.1002/cpt1979266766.
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Species differences of amobarbital metabolism: dihydroxyamobarbital formation.异戊巴比妥代谢的种属差异:二羟基异戊巴比妥的形成
Can J Physiol Pharmacol. 1980 Oct;58(10):1167-9. doi: 10.1139/y80-176.
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Variation in amobarbital metabolism: evaluation of a simplified population study.异戊巴比妥代谢的变异:一项简化人群研究的评估
Clin Pharmacol Ther. 1983 Aug;34(2):202-6. doi: 10.1038/clpt.1983.153.
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A multi-dose study on the human metabolism of amylobarbitone.一项关于异戊巴比妥人体代谢的多剂量研究。
Xenobiotica. 1979 Apr;9(4):205-8. doi: 10.3109/00498257909038722.
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Amobarbital metabolism in man: N-glucoside formation.人异戊巴比妥的代谢:N-葡萄糖苷的形成。
Res Commun Chem Pathol Pharmacol. 1978 Jul;21(1):45-53.
9
The occurrence of two hepatic microsomal sites for amobarbital hydroxylation.异戊巴比妥羟基化的两个肝微粒体位点的存在。
Can J Physiol Pharmacol. 1983 Jan;61(1):67-71. doi: 10.1139/y83-007.
10
Maternal and neonatal elimination of amobarbital after treatment of the mother with barbiturates during late pregnancy.在妊娠晚期用巴比妥类药物治疗母亲后,母亲和新生儿对异戊巴比妥的消除情况。
Clin Pharmacol Ther. 1976 Mar;19(3):271-5. doi: 10.1002/cpt1976193271.

引用本文的文献

1
Human pharmacogenomics: the development of a science.人类药物基因组学:一门科学的发展
Hum Genomics. 2004 Aug;1(5):375-80. doi: 10.1186/1479-7364-1-5-375.
2
Phenobarbital N-glucosylation by human liver microsomes.人肝微粒体对苯巴比妥的N-糖基化作用。
Eur J Drug Metab Pharmacokinet. 2004 Jan-Mar;29(1):51-9. doi: 10.1007/BF03190574.
3
Molecular genetics of cytochrome P450 IID. Anomalies of drug metabolism.细胞色素P450 IID的分子遗传学。药物代谢异常。
Clin Rev Allergy Immunol. 1995 Fall;13(3):211-21. doi: 10.1007/BF02771762.
4
Multidose studies in the human metabolism of pentobarbitone.戊巴比妥人体代谢的多剂量研究。
Eur J Drug Metab Pharmacokinet. 1980;5(2):75-80. doi: 10.1007/BF03189449.
5
An assessment of short-cut procedures for studying drug metabolism in vivo using amobarbital as a model drug.以异戊巴比妥为模型药物对体内药物代谢研究的捷径程序进行评估。
Eur J Clin Pharmacol. 1982;22(3):229-33. doi: 10.1007/BF00545220.
6
The fate of phenobarbitone in children in hypothermia and at normal body temperature.
Can Anaesth Soc J. 1982 Jan;29(1):16-23. doi: 10.1007/BF03007942.
7
Assessment of the drug metabolism capacity of the liver.肝脏药物代谢能力的评估。
Br J Clin Pharmacol. 1982 Nov;14(5):631-51. doi: 10.1111/j.1365-2125.1982.tb04950.x.
8
Stereochemical characterization of the diastereomers of the amobarbital N-glucosides excreted in human urine.人尿中排泄的异戊巴比妥N-葡萄糖苷非对映体的立体化学特征。
Pharm Res. 1990 Aug;7(8):794-800. doi: 10.1023/a:1015900629690.
9
Ethnic differences in drug disposition and responsiveness.药物处置和反应性的种族差异。
Clin Pharmacokinet. 1991 May;20(5):350-73. doi: 10.2165/00003088-199120050-00002.