Metabolism of (-)-(S)-nicotine in the isolated perfused rabbit lung

被引：5

作者：

Aislaitner, G ^{[1
]}

Bello, A ^{[1
]}

Tan, SC ^{[1
]}

Hutt, AJ ^{[1
]}

Marriott, C ^{[1
]}

Gorrod, JW ^{[1
]}

机构：

[1] Univ London Kings Coll, Chelsea Dept Pharm, London, England

来源：

EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS | 1997年 / 22卷 / 04期

关键词：

nicotine; metabolism; isolated perfused lung model; C-14]-cyanide trapping technique; radiolabelled cyanonicotines;

D O I：

10.1007/BF03190976

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The metabolism of (-)-(S)-nicotine has been investigated following intratracheal administration to the recirculating perfused rabbit lung model. The metabolic products present in the perfusate were identified by co-chromatography (HPLC and GC) with authentic standards and quantified by HPLC. After the 180 min perfusion period, nicotine was found to be metabolically transformed to cotinine (33.7%), 3-hydroxycotinine (10.4%), cotinine-1-N-oxide (3.4%) and nicotine-1'-N-oxide (14.4%). Norcotinine, nornicotine, 3-pyridyl-4-oxo-N-methylbutyramide and an uncharacterised metabolite were also detected in low amounts. Following the perfusion experiment, part of the lung tissue was homogenised in the presence of [C-14]-sodium cyanide. Subsequent analysis of the homogenates indicated the formation of 2'-cyanonicotine, 1'-cyanomethylnornicotine and the diastereoisomeric 5'-cyanonicotines.

引用

页码：395 / 402

页数：8

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