The single dose kinetics of (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (
etozolin) and its active metabolite
ozolinone were determined in 6 healthy volunteers, in 12 patients with acute
hepatitis and in 15 patients with
hepatic cirrhosis with
ascites. In
hepatitis, the elimination half-life of
etozolin was 4 times longer resulting in a 2 fold rise in the AUC. At the same time, plasma levels of
ozolinone were lower and consequently the AUC of his metabolite was reduced. In
cirrhosis, the plasma level time curves of
etozolin and
ozolinone differed significantly from the controls and also from those of the patients with acute
hepatitis. For
etozolin Cmax was reduced to about 1/2, the elimination half-life being increased by
a factor of 5. This resulted in a 3 fold higher AUC. As for
ozolinone the reduction of plasma levels was more pronounced--Cmax fell to 1/6 of the control value--so that in spite of a longer elimination half-life, the AUC fell to 1/2.
Ascites concentrations of
etozolin and
ozolinone were almost identical to the plasma concentration. The results suggest that acute
hepatitis and
hepatic cirrhosis lead to a reduced formation of
ozolinone. As a result,
etozolin accumulates and plasma levels of oxolinone drop. Moreover, both substances enter the
ascites to a significant degree. It is concluded that these changes in the kinetics of this lipophilic
diuretic do not allow a reliable dosage regimen in patients with
hepatic cirrhosis and
ascites.