Influence of acute viral hepatitis on phenytoin kinetics and protein binding

Abstract

Patients with liver disease are thought to have abnormal responses to drugs metabolized by the liver, although supportive evidence is sparse. The influence of acute viral hepatitis on the pharmacokinetics and protein binding of phenytoin (DPH) was examined in 5 patients. A longitudinal study design was used so that each patient acted as his own control. DPH clearance was unaffected by acute viral hepatitits over theconcentration range studie, but the percentage of unboudn DPH increased by an average of nearly one-third during acute viral hepatitis. A small decline in serum albumin concentration and elevated serum bilirubin levels may be responsible for the alterations in protein bindig. These results indicate that acute inflammatory liver disease has complex and perhaps paradoxical effects on durg disposition. Clinical and laboratory observations including plasma durg concentrations, still provide the best means for adjusting dosage regimens in patients with fluctuating hepatic function.