Metabolic fate of geranylgeranylacetone.

Abstract

The metabolic fate of 14C-geranylgeranylacetone (GGA), a newly developed antiulcer drug, was investigated in rats. Radioactivity was mainly absorbed by a lymphatic route after the oral administration of 14C-GGA. The recoveries of radioactivity in thoracic lymph were 38 % (administered dose of 1 mg/kg) and 28 % (10 mg/kg) during 8 hr after dosing, and 27 % (125 mg/kg) during 24 hr post dosing. Radioactivity in the lymph collected for 24 hr (125 mg/kg) was present as unchanged GGA (85 %) and two metabolites. These metabolites were isolated in liver extract other as esterified GGA-OH. Tissue and plasma levels or GGA and its metabolites were estimated by TLC after oral or intravenous administration. GGA was rapidly metabolized in liver to GGA-OH, esterified GGA-OH, and other polar metabolites. The tissue concentration of GGA in liver was low, whereas the level of GGA-OH was higher than in plasma. In contrast, the concentration of GGA in the target tissue, stomach, was higher than that in plasma and liver. The concentration of GGA-OH in the stomach was much higher than the plasma level. These results indicate that GGA is distributed systemically in the mucosal cells without a first pass effect owing to its absorption route.