Noninvasive Assessment In Vivo of Hepatic Drug Metabolism in Health and Disease

Despite the availability of techniques and concepts for examining the physiologic processes of drug disposition and clearance by the liver in normal subjects and in patients with liver disease, important questions remain in this field. Major problems include high inducibility of hepatic drug-metabolizing enzymes, even in patients with liver disease (normal drug clearances can occur in liver disease patients who chronically ingest drugs that induce these enzymes); poor correlation between routine liver function tests, such as SGOT, SGPT, alkaline phosphatase, and bilirubin, and alterations of hepatic drug metabolism in hepatocellular disease; failure of all drugs to be similarly affected in liver disease, even for drugs with similar metabolic pathways. Nevertheless, certain test drugs, such as antipyrine and aminopyrine, whose clearances from plasma or saliva closely reflect their hepatic metabolism, may serve as probes to explore under normal and disease conditions how drugs are handled in the liver. Nevertheless, limitations in the use of antipyrine and aminopyrine metabolism as tests of hepatic function must be recognized: special conditions of patients may render results of these tests by themselves impossible to interpret. Utilizing additional drug substrates and measuring rates of formation of individual metabolites, as well as disappearance of parent drug, investigators may be able to research more effectively and in greater detail for interrelationships between liver disease and the processes of hepatic drug metabolism, hepatic blood flow, and even other, as yet unidentified, processes that influence liver and drugs interactions.