title: Trans-3'-hydroxycotinine: disposition kinetics, effects and plasma levels during cigarette smoking.
abstract: OBJECTIVE
  (3'R,5'S)-trans-3'-hydroxycotinine (3-HC) is a major metabolite of nicotine. The aim of this study was to characterize the disposition kinetics of 3-HC in healthy smokers, including metabolism to (3'R,5'S)-trans-3'-hydroxycotinine glucuronide (3-HC-Gluc). We also studied pharmacologic responses to 3-HC and plasma levels of 3-HC in a group of smokers.
  
  
  METHODS
  Eight cigarette smokers were studied on a clinical research ward. After 5 days of supervised nonsmoking, each subject received an intravenous infusion of 3-HC, 4 microg x kg(-1) x min(-1) for 60 min. Plasma and urine levels of 3-HC and 3-HC-Gluc and cardiovascular and subjective responses were examined. Plasma levels of 3-HC, nicotine, and cotinine were measured in 62 smokers on up to three occasions.
  
  
  RESULTS
  The total plasma clearance of 3-HC averaged 1.3 ml x min(-1) x kg(-1), of which 63% was renal excretion of unchanged drug. An average of 29% of the dose was excreted as 3-HC-Gluc. 3-HC did not have nicotine-like cardiovascular effects.
  
  
  CONCLUSIONS
  These findings extend our understanding of the quantitative nature of nicotine metabolism. Such data may be of use in quantitating human exposure to nicotine from tobacco and in studying individual variability in nicotine metabolism.
authors.affiliation: Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center,and the Department of Medicine, University of California, San Francisco, California 94143-1220, USA. nbeno@itsa.ucsf.edu
authors.forename: N L
authors.initials: NL
authors.lastname: Benowitz
authors.forename: P
authors.initials: P
authors.lastname: Jacob
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D003367:Cotinine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000097:blood; D012907:Smoking / Q000097:blood / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C001381:hydroxycotinine; D009538:Nicotine; D003367:Cotinine