Abstract
Influence of liver disease on metabolism and pharmacokinetics of cephalothin (CET) was studied. CET was given 1g bolus intravenously to 7 patients with liver cirrhosis, 7 patients with hepatitis (3 cases of acute hepatitis and 4 of chronic active hepatitis) and 7 patients with normal liver function. Serum consentration of CET and deacetyl CET was measured by High Performance Liquid Chromatography.
Ratio of deacetyl CET to CET was less in cirrhosis compared to that in hepatitis or control group, demonstrating impaired metabolism of CET to deacetyl CET in cirrhosis. Deacetyl CET/CET ratio was correlated to such liver function test as BSP retention rate, prothrombin time or serum γ -globulin level which were characteristic in chronic liver disease, while not correlated to GP T, GOT, γ -GTP, total bilirubin which are characteristic in acute hepatic parenchymal disorders.
Pharmacokinetic parameters calculated as two compartment open model were not statistically different among three groups.
These results show that severe chronic liver disease impairs the biotransformation of CET to deacetyl CET, but does not affect pharmacokinetics of CET.
