[Pharmacokinetic changes in obesity]

Abstract

The obesity-induced kinetic changes have been studied only from twenty years, despite the frequency of such a pathological state; thus many work need to be done in this area. The tissular distribution of drugs may depend on the obesity-induced changes in the body composition taking into account the degree of drug liposolubility. Some other factors such as protein binding and regional blood flow may also be involved in tissular diffusion of drugs in obesity. Drug binding to albumin does not seem to be modified in obesity. On the contrary, the protein binding of some basic drugs is increased because of the rise of the plasma alpha 1 glycoprotein acid levels in obesity. Although the cardiac output and the total blood volume are increased in obese patients, the blood flow recalculated according to the adipose tissue weight, is less than in non obese subjects: this point could reduce the diffusion of some lipophilic drugs. More complex are the obesity induced changes in the hepatic clearance of drugs: some reactions such as oxydo-reduction and acetylation do not vary, some others such as sulfoconjugation or glucuronoconjugation are increased. The renal clearance is increased for drugs totally eliminated by glomerular filtration and for drugs which are both filtrated and secreted. According to the liposolubility characteristic of a drug and its clearance, one can calculate the loading dose and the maintenance dose.