Serum protein and lipid concentrations as well as the serum protein binding of propranolol, diazepam and phenytoin were measured in normal weight and obese volunteers. Concentrations of alpha 1‐acid glycoprotein (AAG) in the obese subjects were double that of the lean controls. Conversely, concentrations of high density lipoproteins (HDL) were decreased in the obese group. The serum binding of propranolol was increased in the obese subjects and correlated with serum AAG concentrations. Diazepam binding was slightly decreased in the obese as a result of lower serum albumin concentrations and elevated free fatty acids. The binding of phenytoin was comparable in all of the volunteers. These findings point out some of the complex pathophysiologic changes associated with obesity which may in turn influence drug disposition and hence drug therapy in the obese patient.

Although clinically relevant, drug-protein interactions in the morbidly obese population have not been studied thoroughly. The objective of this study was to evaluate serum chemistry profiles and the degree of serum protein binding of propranolol, diazepam and phenytoin in the serum of four female, morbidly obese (> 190% of ideal body weight) and eight control female subjects. Serum triglyceride concentrations were higher and high-density lipoproteins were lower in the obese subjects than in the control group. Serum albumin and total protein concentrations in the obese were not different from controls. Unexpectedly, a,-acid glycoprotein concentrations were doubled in the obese subjects (mean obese value 121 mg 100 ml vs 62.9 mg, 100 ml for the control subjects). Obese subjects had a mean fraction unbound (fu) for propranolol of 0.086, which was significantly different from the controls (f, = 0.123). The binding of diazepam was decreased slightly in the obese subjects. The binding of phenytoin was similar in both groups.The altered serum chemistry of obesity may play a significant role in the drug management of the obese patient by altering drug-protein interactions.

The influence of smoking an alpha 1-acid glycoprotein (alpha 1-AGP) and serum albumin concentrations and the protein binding of phenytoin and propranolol in healthy volunteers was investigated. alpha 1-AGP concentrations were found to be statistically different (P less than 0.05) in the smokers (mean = 84.3 mg dl-1) versus non-smokers (mean = 62.8 mg dl-1). There was a trend for lower serum albumin concentrations and lower fraction unbound of propranolol in the smokers. Smoking did not affect the protein binding of phenytoin.

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