The pharmacokinetic profile of ochratoxin A in the rat after oral and intravenous administration.

A single oral or iv dose (2.5 mg/kg) of ochratoxin A was administered to healthy adult rats. A spectrofluorimetric method was used to determine the toxin level in plasma. The results suggest that the toxin is distributed in two kinetically distinct body compartments. By use of computer techniques, values were assigned to the pharmacokinetic parameters for ochratoxin A in the rat. The half-life of the drug was around 55 hr for either oral or iv administration. Digital computer-simulated curves of the toxin levels in the central and peripheral compartments as well as a total elimination curve were generated. When 14C-ochratoxin A was administered to rats, there were peaks of radioactivity 1 and 6 hr after injection. Ochratoxin alpha was the only metabolite recovered from the cecum and large intestine. Ochratoxin A was excreted via urine and feces, both as the free drug and hydroylzed to ochratoxin alpha; in urine there were five unidentified labeled metabolites. Some of the water-soluble radioactivity was not recovered in the acidic ether extract of the excreta. A hierarchical clustering technique was used to classify the organs in central and peripheral compartments. Muscle, fat, and skin were found to belong to the deep compartment. The residue problem is discussed.