Tiopinac absorption, distribution, excretion, and pharmacokinetics in man and animals

[14C]Tiopinac disposition was evaluated in man, monkey, rabbit, mouse, minipig, and rat. The absorption of tiopinac was rapid and essentially complete in these species. Peak plasma levels occurred in less than 1 hr to 2 hr in all species. Following iv and po doses, tiopinac was recovered predominantly in the urine. In man, 93.2 and 2.6% of the administered radioactivity was recovered in the urine and feces, respectively. In the rat, 61.3% of the radioactivity was accounted for in urine and 32.7% in feces. In the mouse, radioactivity was concentrated in the kidney and liver, with tissue/plasma ratios ranging from 1.3 to 7.0 for kidney and 0.5 to 1.7 for liver. Radioactivity in all other tissues was generally lower than in plasma. Tiopinac was shown to be the major circulating entity in plasma, accounting for 90% of total radioactivity levels in the mouse and 61% in the rat. The half-life of tiopinac was 2.3 +/- 0.3 hr in man, 0.8 hr in the minipig, and 2.6 hr in the rabbit. The volume of distribution was 0.29 +/- 0.05 liter/kg in man, 0.16 liter/kg in the rabbit and minipig, and 0.42 liter/g in the mouse. Tiopinac was highly bound (99.5%) in human serum.