A study of esterase--its application to biotransformation of midecamycin derivatives

Esterases of intestinal mucosa and liver from human and rat were used to study the biotransformation of midecamycin derivatives. In the in vitro experiment with rat esterases, the 4"-acyl derivatives were more easily hydrolyzed than the 9-acyl derivatives. Among the 9-acyl esters, the highest hydrolytic activity was observed with butyrate. In the in vivo experiment, when the rats were administered with the derivatives of 4"-depropionylmidecamycin (M1) orally, comparatively more 9-acyl metabolites were excreted in the urine, but the amount of the 4"-acyl metabolites was very small. In the in vitro experiment with human esterases, the 9-acyl esters were hydrolyzed more easily than the 4"-acyl esters. Among the 9-acyl esters of M1, the highest hydrolytic activity was observed with butyrate. When the 9-acyl esters were administered to humans, the n-butyl ester was hydrolyzed faster than the acetyl ester. When the 9,4"-diacetyl ester was administered to humans, comparatively more 4"-acyl metabolites were excreted in the urine. These results suggest that the experiment with the use of these esterases is useful to estimate the biotransformation of midecamycin derivatives.