Factors influencing diazepam pharmacokinetics: age, sex, and liver disease

Published data on the effect of cirrhosis on diazepam pharmacokinetics were reanalyzed to determine how age, sex, and body weight might have influenced the conclusions. Diazepam elimination half-life (t1/2beta) and weight-corrected volume of distribution (Vd) were significantly larger in patients with cirrhosis (n = 9) than in controls (n = 4). Weight-corrected diazepam clearance was significantly reduced in cirrhotics as compared with controls. Multiple stepwise regression analysis, however, revealed that age and liver disease were of approximately equal importance as determinants of t1/2beta. Age, sex, and liver disease all influenced Vd, but liver disease by far was the most important determinant of diazepam clearance. Thus age, sex, and body size can have an important influence on the pharmacokinetics of drugs, and should be included as independent variables in pharmacokinetic studies.