The demethylation of amitriptyline administered by oral and intramuscular routes

A single intramuscular (IM) dose of 50 mg amitriptyline (AT) was given to each of two healthy subjects who had previously taken three oral doses of AT tablets. The concentration-time curves of plasma nortriptyline (NT) arising from IM AT were fitted by computer to an equation based on the assumptions that NT is produced at a rate proportional to plasma AT concentration and is eliminated at a rate proportional to plasma NT concentration. The total amount of systemic NT produced was approximately equal for IM and oral AT doses, suggesting that the hepatic elimination of a given quantity of AT produces a constant amount of systemic NT, whether the AT is metabolised in the first pass or from the systemic circulation. This conclusion is supported by analysis of the time course of plasma NT concentration arising from oral AT doses. A large early production had previously been demonstrated and attributed to first-pass metabolism. The proportion of each oral AT dose eliminated in the first pass could now be estimated. Values ranged from 51% to 70% and were approximately equal to the proportion of the total NT apparently formed in the first pass.