The pharmacokinetics and tissue concentrations of cyclohexylamine in rats and mice.
Cyclohexylamine showed dose-dependent kinetics after administration of single oral doses up to 500 mg/kg in rats, with a reduction in plasma clearance, an increase in apparent half-life, and an increased area under the testicular concentration-time curve. Cyclohexylamine was absorbed and eliminated more rapidly by mice. Saturation of cyclohexylamine uptake by rat renal cortical slices in vitro and of renal tubular secretion in vivo occurred at concentrations and doses comparable to the oral dose studies. During chronic dietary administration the concentrations of cyclohexylamine in the plasma and testes showed a pronounced diurnal variation in rats which was not detected in mice. The steady-state plasma clearance in rats was approximately one-half that in mice. The concentrations of cyclohexylamine in the plasma and testes of rats, but not mice, showed a nonlinear relationship to dietary intake. Elevated concentrations were found at intakes greater than 200 mg/kg/day. The pharmacokinetics of cyclohexylamine make an important contribution to the difference in sensitivity to testicular atrophy in rats and mice and the dose-response relationship for this toxicity in rats.
Roberts
A
A
Clinical Pharmacology Group, University of Southampton, Bassett Crescent East, United Kingdom.
Renwick
A G
AG
D000818:Animals; D002940:Circadian Rhythm; D003494:Cyclamates / Q000633:toxicity; D003514:Cyclohexylamines / Q000493:pharmacokinetics* / Q000633:toxicity; D006207:Half-Life; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013737:Testis / Q000378:metabolism
D003494:Cyclamates; D003514:Cyclohexylamines