Methods of the assessment of the effect of drugs on liver blood flow in man.

Abstract

The liver is the central metabolic organ of the body and therefore the volume and the composition of the blood perfusing the liver are undoubtedly major determinants of hepatocellular function. In the past the amount of liver blood flow and its regulation was mainly investigated by physiologists and most of the work was done in animals (Bradley, 1963; Greenway and Stark, 1971). In recent years clinicians and pharmacologists have paid more attention to the problem of liver blood flow measurements as it was found that drug metabolism can be influenced by changes in liver blood flow under certain experimental conditions (Ohnhaus, Thorgeirsson, Davies and Breckenridge, 1971; Branch, Shand, Wilkinson and Nies, 1974). Based on these findings a physiological approach to hepatic drug clearance has been developed which seems very useful in predicting changes in drug kinetics produced by variations in the biological determinants of drug disposition (Wilkinson, 1975; Wilkinson and Shand, 1975). In addition, as surgeons started to treat portal hypertension occurring in liver disease such as cirrhosis by portocaval or similar anastomoses, liver blood flow was assessed with other parameters of liver function to select appropriate patients for surgery (Bircher, Blankart, Halpern, Hacki, Laissue and Preisig, 1973). These facts have increased tremendously the interest of clinical pharmacologists and clinicians in the methods for liver blood flow measurement and their limitations in order to investigate changes in drug metabolism under certain clinical and experimental conditions and the clinical outcome of liver disease following different operating procedures.