Enantioselective metabolism during continuous administration of S-(-)- and R-(+)-nicotine isomers to guinea-pigs

J Pharm Pharmacol. 1988 Dec;40(12):862-9. doi: 10.1111/j.2042-7158.1988.tb06289.x.


The S-(-)- and R-(+)-nicotine isomers were administered subcutaneously via Alzet osmotic pumps to male Hartley guinea-pigs (n = 5 with each isomer) over a 23-day period. Estimated dosage rate throughout the experiment was 0.6 mg-1. Urine samples were collected over this time and the levels of urinary oxidative and N-methylated nicotine metabolites were measured by cation-exchange HPLC analysis. S-(-)-Nicotine formed only oxidative metabolites, whereas the R-(+)-isomer formed both oxidative and N-methylated metabolites. 3'-Hydroxycotinine and nicotine-1'-oxide were major metabolites of both enantiomers; cotinine and nornicotine were only minor metabolites. The major N-methylated metabolite of R-(+)-nicotine was N-methylnicotinium ion; N-methylcotininium ion and N-methylnornicotinium ion were also identified as metabolites of this nicotine isomer. Total N-methylated quaternary ammonium metabolites accounted for 15 to 20% of the administered dose of R-(+)-nicotine. An interesting enantioselective reduction in the percent of oxidative urinary metabolites formed S-(-)-nicotine was observed over 23 days. This may indicate the enantioselective induction of an uncharacterized metabolic pathway for this nicotine isomer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotransformation
  • Chromatography, Gas
  • Chromatography, High Pressure Liquid
  • Cotinine / analogs & derivatives
  • Cotinine / analysis
  • Cotinine / isolation & purification
  • Cotinine / metabolism
  • Guinea Pigs
  • Male
  • Nicotine / metabolism*
  • Stereoisomerism
  • Time Factors


  • hydroxycotinine
  • Nicotine
  • Cotinine