Pharmacokinetics of lidocaine in perfused rat liver

Lidocaine pharmacokinetics were studied using perfused rat livers under several conditions. 1) In the low perfusion group (perfusion rate = 1/2 of control group), the elimination rate constant and clearance of lidocaine in the first phase were reduced, but in the second phase, metabolism of lidocaine was more active than in other groups. 2) High albumin concentration in the perfusate did not significantly affect lidocaine metabolism. 3) Low pH of the perfusate (pH = 7.10) did not affect the metabolism of lidocaine. 4) Acute and chronic liver damage inhibited the lidocaine metabolism, which may be due to decreases in viable hepatocytes, effective hepatic blood flow and mitochondrial P-450. 5) Halothane in the concentration of 2.5% reduced the lidocaine metabolism. This was probably due to inhibition of hepatocyte activity by halothane because increases in GOT, LDH and lactate in the perfusate and a decrease in the O2 consumption by the rat liver were observed.