Drug Distribution in Obesity and following Bariatric Surgery: A Literature Review

Background: The pharmacokinetic variables of drug clearance and volume of distribution are usually corrected for body weight or surface area. Only recently have the relationships which exist between body size, physiologic function and pharmacokinetic variables been evaluated in the obese population. These effects are not widely known, and data on this and the effects of bariatric surgical procedures are scantily documented in the surgical literature. Methods: Literature review. Results: Drugs with a low or moderate affinity for adipose tissue have a moderate increase in the volume of distribution (Vd), and this correlates with the increase in lean body mass (LBM). Highly lipophilic drugs, with some exceptions, show the expected increase in Vd and prolongation of elimination half-life, indicating a marked distribution into adipose tissue. Drug absorption, in general, is slowed by delayed gastric emptying and is normal when gastric emptying is normal or increased. Most drug absorption occurs in the small intestine where duration of drug/mucosal contact is the most important factor. Conclusions: Drugs whose distribution is restricted to LBM should utilize a loading dose based on ideal body weight (IBW). For those drugs which distribute freely into adipose tissue, the loading dose should be based on total body weight (TBW). Adjustment of the maintenance dose depends on clearance rates. In a few cases dosage adjustment depends on pharmacodynamic data, since drug clearance does not conform to these recommendations, for reasons which remain to be defined. Following bariatric surgery, in the absence of delayed gastric emptying or uncontrolled diarrhea, drug absorption rates are usually comparable to the non-operated patient.