Trans-3′-hydroxycotinine:: Disposition kinetics, effects and plasma levels during cigarette smoking

被引:91
作者
Benowitz, NL
Jacob, P
机构
[1] Univ Calif San Francisco, Dept Med, Div Clin Pharmacol & Expt Therapeut, San Francisco, CA 94143 USA
[2] San Francisco Gen Hosp, Med Ctr, Med Serv, Div Clin Pharmacol & Expt Therapeut, San Francisco, CA 94110 USA
[3] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA
关键词
3 '-hydroxycotinine; cotinine; metabolism; nicotine; pharmacodynamics; pharmacokinetics; smoking; tobacco;
D O I
10.1046/j.1365-2125.2001.01309.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aims (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 mug kg(-1) 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 mi min(-1) 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.
引用
收藏
页码:53 / 59
页数:7
相关论文
共 27 条
[1]  
[Anonymous], 1972, The dependability of behaviourial measurements: Theory of generalzsability for scores and profiles
[2]  
Armstrong DW, 1998, CHIRALITY, V10, P587, DOI 10.1002/(SICI)1520-636X(1998)10:7<587::AID-CHIR6>3.0.CO
[3]  
2-#
[4]   NONCOMPARTMENTAL DETERMINATION OF THE STEADY-STATE VOLUME OF DISTRIBUTION [J].
BENET, LZ ;
GALEAZZI, RL .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1979, 68 (08) :1071-1074
[5]   METABOLISM OF NICOTINE TO COTININE STUDIED BY A DUAL STABLE-ISOTOPE METHOD [J].
BENOWITZ, NL ;
JACOB, P .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1994, 56 (05) :483-493
[6]  
BENOWITZ NL, 1994, J PHARMACOL EXP THER, V268, P296
[7]   Sources of variability in nicotine and cotinine levels with use of nicotine nasal spray, transdermal nicotine, and cigarette smoking [J].
Benowitz, NL ;
Zevin, S ;
Jacob, P .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1997, 43 (03) :259-267
[8]   SMOKERS OF LOW-YIELD CIGARETTES DO NOT CONSUME LESS NICOTINE [J].
BENOWITZ, NL ;
HALL, SM ;
HERNING, RI ;
JACOB, P ;
JONES, RT ;
OSMAN, AL .
NEW ENGLAND JOURNAL OF MEDICINE, 1983, 309 (03) :139-142
[9]  
BENOWITZ NL, 1991, ADV PHAR SC, P19
[10]  
BOWMAN ER, 1962, J PHARMACOL EXP THER, V135, P306