Abstract
Gastrointestinal absorption of CS-600 was shown to be rapid and almost quantitative in rats. The cyclopentanone moiety of CS-600 was reduced rapidly to afford a mixture of trans-OH and cis-OH as principal metabolites in plasma of rats, dogs and monkeys. The plasma levels of trans-OH having strong inhibitory activity for PG synthetases was 2-3 times higher than that of cis-OH. The stereochemistry of trans-OH isolated from rat urine was established to be a single SRS-configuration, indicating the stereospecific reduction of the cyclopentanone moiety. The CS-600 reducing enzyme was purified from rabbit liver cytosol fraction as single protein and shown to be one of the aromatic aldehyde-ketone reductases on the basis of substrate specificity, effects of inhibitors, optimal pH (6.2), cofactor requirement (NADPH) and molecular weight (ca. 33, 000) .
