Studies on the metabolism of l-menthol in rats

Drug Metab Dispos. 1988 Sep-Oct;16(5):765-72.


Metabolism of l-menthol in rats was investigated both in vivo and in vitro. Metabolites isolated and characterized from the urine of rats after oral administration (800 mg/kg of body weight/day) of l-menthol were the following: p-menthane-3,8-diol (II), p-menthane-3,9-diol (III), 3,8-oxy-p-menthane-7-carboxylic acid (IV), and 3,8-dihyroxy-p-menthane-7-carboxylic acid (V). In vivo, the major urinary metabolites were compounds II and V. Repeated oral administration (800 mg/kg of body weight/day) of l-menthol to rats for 3 days resulted in the increase of both liver microsomal cytochrome P-450 content and NADPH-cytochrome c reductase activity by nearly 80%. Further treatment (for 7 days total) reduced their levels considerably, although the levels were still higher than the control values. Both cytochrome b5 and NADH-cytochrome c reductase levels were not changed during the 7 days of treatment. Rat liver microsomes readily converted l-menthol to p-menthane-3,8-diol (II) in the presence of NADPH and O2. This activity was significantly higher in microsomes obtained from phenobarbital (PB)-induced rats than from control microsomal preparations, whereas 3-methylcholanthrene (3-MC)-induced microsomes failed to convert l-menthol to compound II in the presence of NADPH and O2. l-Menthol elicited a type I spectrum with control (Ks = 60.6 microM) and PB-induced (Ks = 32.3 microM) microsomes whereas with 3MC-induced microsomes it produced a reverse type I spectrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotransformation
  • Chromatography, Gas
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Cytochrome b Group / biosynthesis
  • Cytochromes b5
  • Magnetic Resonance Spectroscopy
  • Male
  • Mass Spectrometry
  • Menthol / metabolism*
  • Menthol / pharmacology
  • Menthol / urine
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism*
  • NADH Dehydrogenase / biosynthesis
  • NADPH-Ferrihemoprotein Reductase / biosynthesis
  • Rats
  • Rats, Inbred Strains
  • Reference Values


  • Cytochrome b Group
  • Menthol
  • Cytochromes b5
  • Cytochrome P-450 Enzyme System
  • NADPH-Ferrihemoprotein Reductase
  • NADH Dehydrogenase