Document Detail


Pharmacokinetics of nicotine, cotinine, and 3'-hydroxycotinine in cigarette smokers.
MedLine Citation:
PMID:  3184779     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The trans-isomer of 3'-hydroxycotinine has recently been identified as a major metabolite of nicotine in urine of cigarette smokers. We, therefore, investigated the pharmacokinetics of 3'-hydroxycotinine in six male smokers after intravenous infusion of nicotine, cotinine, and 3'-hydroxycotinine. Serum concentrations of 3'-hydroxycotinine were lower than those of cotinine throughout the observation period of 60 h after infusion of nicotine or cotinine, whereas the amounts excreted in the urine were similar or higher than those of cotinine. The following means and ranges for the pharmacokinetic parameters were derived from the 3'-hydroxycotinine infusion experiment: half-life (t1/2 beta) = 5.9 (4.2-9.5) h; apparent volume of distribution (Vd) = 0.87 (0.51-1.14) l/kg; total clearance (Cl total) = 1.79 (1.08-2.59) ml/min/kg; renal clearance (Clr) = 1.31 (0.85-1.78) ml/min/kg; percentage of renal clearance (Clr/Cl total) = 75.4 +/- 12.8 (60.3-98.2). The high percentage of renal clearance suggests that further metabolization of this compound is limited. No evidence for a mutagenic activity of 3'-hydroxycotinine or of urine extracts from subjects dosed with hydroxycotinine was found with the S. typhimurium (TA 98) microsome assay.
Authors:
G Scherer; L Jarczyk; W D Heller; A Biber; G B Neurath; F Adlkofer
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Klinische Wochenschrift     Volume:  66 Suppl 11     ISSN:  0023-2173     ISO Abbreviation:  Klin. Wochenschr.     Publication Date:  1988  
Date Detail:
Created Date:  1988-12-21     Completed Date:  1988-12-21     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  2985205R     Medline TA:  Klin Wochenschr     Country:  GERMANY, WEST    
Other Details:
Languages:  eng     Pagination:  5-11     Citation Subset:  IM    
Affiliation:
Forschungsgesellschaft Rauchen und Gesundheit mbH, Hamburg.
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MeSH Terms
Descriptor/Qualifier:
Adult
Cotinine / administration & dosage,  analogs & derivatives,  pharmacokinetics*
Humans
Infusions, Intravenous
Male
Metabolic Clearance Rate
Mutagenicity Tests
Nicotine / administration & dosage,  pharmacokinetics*
Pyrrolidinones / pharmacokinetics*
Smoking / blood*
Chemical
Reg. No./Substance:
0/Pyrrolidinones; 27323-64-4/hydroxycotinine; 486-56-6/Cotinine; 54-11-5/Nicotine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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