Plasma Levels of Imipramine and Desmethylimipramine during Therapy

Abstract

Individual variations in drug metabolism are important factors affecting both toxicity and clinical effectiveness (Brodie, 1964; Kalow, 1965; Price Evans, 1965). In most cases the best available index of the drug concentration at the site of action is the plasma level. An estimate of this will show whether the optimal concentration is present and in some cases may indicate whether new symptoms can be attributed to toxic side reactions.

Rate of Aminopyrine Disappearance from Plasma in Young and Aged Humans

“…These results do not reach a high level of statistical significance to draw definite conclusions, but they suggest that other factors, not necessarily correlated with drug metabolism (8,11,15) may be considered in explaining the higher plasma levels of drugs in females than in males, reported also for other agents by other authors (7,13).…”

Effect of long‐term phenothiazine treatment on drug metabolism.

“…Moody, Tait & Todrick (1967) found that the administration of phenothiazines to patients chronically treated with tricyclic antidepressants increased the steady-state plasma levels of the latter. A similar effect on diphenylhydantoin levels has been mentioned by Kutt & McDowell (1968).…”

Plasma Concentrations of Tricyclic Antidepressive Drugs

“…Also, the ratio between the tertiary amine and its secondary amine metabolite (e.g. imipramine/desipramine ratio) differs substantially among individuals (Moody, Tait & Todrick, 1967). Much of this variation is genetically determined (Alexanderson, Price Evans & Sj6qvist, 1969).…”

“…There have been far fewer studies of imipramine but, again, great inter-individual variation in plasma concentration has been found and lack of clinical response is associated with low plasma concentrations (Moody et al, 1967;Walter, 197 1).…”