The metabolism and binding of [14C]mycophenolic acid in the rat

Abstract

Seventeen h after the intraperitoneal administration of 33 mg/kg of [14C]mycophenolic acid to rats, radioactivity was bound to the tissues of the intestines, bladder, stomach, kidney, liver and lung in decreasing order; no binding to spleen tissue was observed. In vitro incubations of the agent with macromolecules resulted in the binding of radioactivity to salmon sperm DNA and to bovine plasma albumin, the extent of binding being increased and decreased, respectively, in the presence of a rat liver microsomal system. The binding was apparently covalent since repeated purification procedures failed to release the bound radioactivity; heating of [14C]mycophenolic acid bound-DNA in n hydrochloric acid at 100° for 2 h caused the release of the bound radioactivity. Under the conditions described, 43% of the administered radioactivity was excreted in the urine (33%) and faeces (10%); the urine contained free mycophenolic acid (13%), mycophenolic acid glucosiduronate (17%) and an uncharacterized metabolite (3%).