Disposition of [4-14C]mofebutazone in the rat

Abstract

The absorption and elimination of radioactivity after the oral or intraperitoneal administration of[4-14C]mofebutazone was studied in rats. The blood concentration of radioactivity reached a maximum after about 0.7 h, fell rapidly until about 2 h, and then declined slowly. There was sometimes a second peak between 3-6 h. Elimination of radioactivity in urine and feces was extensive and rapid. Over a 24 h period, 73% of the orally administered radioactivity was eliminated in the urine and 15% in the faeces; most of this was eliminated during the first 8 h (89% of the urine radioactivity, 56% of the faeces radioactivity). In anaesthetized rats with cannulated bile ducts, 94% of the intraperitoneally injected radioactivity was eliminated in the bile over a 6 h period. Most of the radioactivity (about 85%) eliminated in the bile and the urine was in the form of a glucuronide and only small amounts less than 10%, was in the form of mofebutazone.

Pharmacokinetics of [4-14C] Mofebutazone after oral administration in man

“…Common to both man and rat are the biexponential character of the elimination phase and the dominance of conjugation as a major pathway of elimination (7,8).…”

“…Specifications of [4_ 14C] mofebutazone were previously described (7). The specific activity was 69.7…”

“…Thin-layer chromatography of ..the 24 h urine (solvent system n-butanol-glacial acetic acid-water 4:1 :1; v/v/v) and measurement of radioactivity were carried out according to previously described methods (7). Blood and urine samples were counted in a mixture of Triton X 100: toluene (I :2) containing glacial acetic acid (0.7%), PPO (0.5%) and POPOP (0.02%).…”

“…More recently, the disposition of the drug in rat has been studied (7,8). These investigations pointed to marked differences in the pharmacokinetics of ' *" Registered trade mark: Mofesal't ; Producer, Medice…”