Species difference in hypertriglyceridemia and hepatic drug-metabolizing enzyme induction by amitriptyline

Prolonged use of tricyclic antidepressants is known to produce hypertriglyceridemia in human subjects. In the present experimental study, species difference of amitnptyline (AT) -induced hypertriglyceridemia in rabbits, rats, mice and guinea pigs and the effect of AT on hepatic microsomal aminopyrine N-demethylase induction (an index of hepatic microsomal activity) in rats were investigated. Significant and consistent increases in serum triglyceride (TG) levels were noted after 2-week oral administration of AT (30 mg/kg/day) in rabbits and rats, while no change in the serum TG levels occurred in mice and guinea pigs. Repetitive oral administration of AT (30 mg/kg/day) to rats for 2 weeks significantly increased the aminopyrine N-demethylase activity. Our results indicate the species difference in AT-induced hypertriglyceridemia by the different AT metabolism processes and suggest the possibility that the hypertriglyceridemia might be related to the induction of the hepatic microsomal enzymes, influencing on TG synthesizing pathway.