The Metabolism and Pharmacokinetics of Clomipramine (Anafranil)

Introduction The behaviour of a drug in the body, ie its absorption, distribution, metabolism and excretion depends on two factors: firstly the physico-chemical properties of the active substance and, secondly, the way in which the organism reacts to it. Although much detailed information may be available about both these factors, it is still impossible to predict precisely and quantitatively how a new substance will behave in the organism. The most that can be done is to make a few qualitative pre-suppositions based on the structure and physico-chemical properties of the substance. Clomipramine, the active substance of Anafranil® (Fig 1) is an organic base with a tricyclic skeleton of highly lipophilic nature. It can therefore be expected to display a distribution pattern characterized by higher concentrations in those tissues and organs exhibiting an affinity for lipophilic bases, eg the lungs, adrenals and kidneys. The compound is likely to pass easily through the lipophilic membranes and barriers of the body giving rapid intestinal absorption and distribution in the organism. Furthermore, it can be assumed that the lipophilic molecule will be transformed to hydrophilic, ie watersoluble metabolites prior to excretion in urine or bile. To what extent these qualitative predictions are accurate and how the substance in fact behaves in quantitative terms can of course only be answered by an experimental study.