Amitriptyline pharmacokinetics. A crossover study with single doses of amitriptyline and nortriptyline.

Six healthy volunteers were given single doses of amitriptyline (AT) and of nortriptyline (NT) separated by at least 10 days. Plasma concentrations of both compounds were measured at intervals for 48 or 72 h. The total areas under the concentration-time curves for the ingested drug were greater for NT, but AT concentrations showed much higher peak values and took more than 12 h to reach the terminal beta phase of elimination. Doses of 50 mg AT produced areas averaging slightly less than half those for 100 mg AT in the same subject, suggesting some saturation of the elimination process. The consumption of a large, fatty meal just before taking the AT tablets had little effect on the plasma drug concentration curves. NT half-lives, measured after ingestion of NT tablets, were used in analysing the production of NT from doses of AT in the same subject. There was a rapid early production, amounting to 30-67% of the total and presumably resulting from the first pass of AT through the liver. NT was then formed continuously at a rate always proportional to the simultaneous rate of AT elimination. The total amount of NT entering the systemic circulation was about one-quarter of the AT dose.