[Hepatic clearance of drugs. Physiological and pharmacokinetic considerations]

The aim of the first part of this work is to present elements of hepatic cytology and physiology in order to demonstrate the organisation of the liver for the metabolisation of drugs: the cytology of hepatocytes, their arrangement in the parenchyma, the hepatic microvascularisation, the distribution of the metabolic reactions in the hepatic acinus and the structure of the biliary tract involved in the elimination of some metabolites. 2. The second part is devoted to the concept of hepatic clearance. A few considerations are presented about physiological aspects (hepatic uptake), followed by a more extensive chapter about pharmacokinetics. The following points are explained: mathematical terms of clearance, physiological models, hepatic first-pass effect, influence of the hepatic clearance on half-life of a drug and area under the curve of concentration versus time, the use of clearance or half-life as index of hepatic metabolism and a classification of the drugs in correlation with their hepatic clearance. 3. The conclusions present some contradictions and unresolved points persisting, at the present time, in the hepatic clearance theories and propose new approaches for future investigations.