Pharmacokinetic considerations in obesity.

Obesity is a disease characterized as a condition resulting from the excess accumulation of body fat. In conjunction with increased stores of body fat, obesity has also been associated with increased mortality influenced by increased incidence of hypertension, atherosclerosis and coronary artery disease, diabetes, cancers of the breast, colon, prostate, endometrium, ovary, and cervix, and decreased overall survivability when compared with nonobese counterparts.1-5 As a consequence, obese individuals generally require more therapeutic intervention earlier in life than nonobese individuals. A very important consideration for pharmacological treatment of obese individuals is the possible discrepancies between obese and nonobese individuals in pharmacokinetic and/or pharmacodynamic activities of a drug. Changes in pharmacokinetic parameters such as volume of distribution or clearance can significantly alter the pharmacologic impact of a drug; therefore, it is important to characterize the properties of drugs in obese individuals. The direct causes of obesity are difficult to discern due to the plethora of physiological changes associated with obesity. Furthermore, characterizing metabolic and genetic differences between obese and nonobese individuals has proven complex resulting in broad scale attempts to study genetic and nutritional models of obesity in animals. These animal models can be used to help determine the possible causes and effects of obesity in humans resulting in possible agents to attenuate the causes and effects of obesity. There have been several references reviewing the causes and pharmacological implications of obesity.6-12 These show the effects of obesity on the pharmacokinetics of drugs in obese subjects; however, there have been considerable advances in the understanding of obesity, particularly in the genetic causes and changes in genetic expression asssociated with obesity. This article will attempt to comprehensively review current knowledge regarding obesity ranging from genetic and nutritional animal studies to pharmacokinetic studies of specific drugs in humans.