Pharmacokinetics of obese adults: Not only an increase in weight

Obesity is a pathophysiological state defined by a body mass index > 30 kg/m² and characterized by an adipose tissue accumulation leading to an important weight increased. Several pathologies named comorbidities such as cardiovascular disease, type 2 diabetes and cancer make obesity the fifth cause of death in the world. Physiological changes impact the four main phases of pharmacokinetics of some drugs and leads to an inappropriate drug-dose. For absorption, the gastrointestinal transit is accelerated, and the gastric empty time is shortened, that can reduce the solubilization and absorption of some oral drugs. The drug distribution is probably the most impacted by the obesity-related changes because the fat mass (FM) increases at the expense of the lean body weight (LBW), leading to an important increase of the volume of distribution for lipophilic drugs and a low or moderately increase of this parameter for hydrophilic drugs. This modification of the distribution may require drug-dose adjustments. By various mechanisms, the metabolism and elimination of drugs are impacted by obesity and should be considered as similar or lower than that non-obese patients. To better understand the necessary drug-dose adjustments in obese patients, a narrative review of the literature was conducted to highlight the main elements to consider in the therapeutic management of adult obese patients.