BIOTRANSFORMATION OF A SOMATOSTATIN ANALOG IN PRECISION-CUT LIVER ANDKIDNEY SLICES FROM RAT, DOG AND MAN

1. Cleavage of the glucopyranosyl moiety of the somatostatin analogue SDZ CO 611 results in the formation of the major metabolite, SDZ CO 61 0, in liver and kidney slices of rat, dog and man, as well as in liver S9 and cytosol of rat and man. 2. The rates of SDZ CO 610 formation ( nmol/h/mg slice protein) for all three species were determined in live r slices for 24 h and the relative order was: rat (0.12) > dog (0.096) = man (0.095). The rates of SDZ CO 610 formation (nmol/h/mg slice pro tein) for all three species in kidney were determined, and the relativ e order was: rat (0.29) > dog (0.16) > man (0.10). 3. SDZ CO 610 was r apidly formed by rat gut contents in the absence of NADPH, possibly by disaccharide-splitting enzymes. 4. Biotransformation of SDZ CO 611 to SDZ CO 610 in human and rat liver S9 and cytosol was similar to that found in liver slices cultures indicating that cleavage of the glucopy ranosyl moiety of SDZ CO 611 could occur in the presence and in the ab sence of cytochrome P450, possibly by glucosidases in liver cytosol. 5 . Rat intestinal homogenate also formed SDZ CO 610 but metabolism was dependent upon NADPH, suggestive of a cytochrome P450-dependent reacti on.