The effect of malnutrition on the pharmacokinetics of phenylbutazone

The pharmacokinetics of phenylbutazone were studied after a single oral dose of 6 mg/kg bodyweight in 35 adult male subjects with differing nutritional status. The elimination half-life was significantly shorter and plasma clearance accelerated in undernourished patients who had significant weight deficit and low serum albumin concentration. Plasma protein binding was only 86% compared with 95 to 96% in normal subjects (smokers and non-smokers). The apparent volume of distribution was also higher in undernourished patients. Significant correlations were observed between serum albumin, protein binding and bodyweight. Multiple regression analysis of the data indicated that altered drug protein binding partially contributed towards variation in half-life and clearance; and the plasma albumin concentration significantly influenced the amount of drug bound in plasma. The results indicate that nutritional status is one of the important environmental variables that can alter drug kinetics and disposition in man. Further studies, including measurement of steady-state plasma concentrations of various other drugs, are necessary to elucidate drug kinetics in malnourished subjects.