Pharmacokinetic study of 2-(2'-methyl-3'-chloro-anilino)-lysine nicotinate (L-104)

The pharmacokinetic study of a new analgesic-antiinflammatory agent, 2-(2'-methyl-3'-chloro-anilino)lysine nicotinate (L-104), was preformed in the rat and the dog. When administered p.o. in rats at a dose of 40 mg/kg, the serum peak was 131.3 microgram/ml +/- 10.3 at 15 min post application, and the elimination t 1/2 was 1.20 h. For the same dose, given i.v., the biological t 1/2 was 1.38 h, the AUC 337.18 microgram/ml/h and the Vdss 0.232 l/kg. When administered i.v. in dogs of 10 mg/kg, the biological t 1/2 was 0.96 h +/- 0.14, the AUC 73,066 microgram/ml/h and the Vdss 0.178 l/kg. In the rat, for a dose of 40 mg/kg given p.o., 79.1% of tritium-labelled L-104 were excreted within 72 h, 56.0% of them through the kidneys. In the dog, at an i.v. dose of 10 mg/kg, the whole of the drug was excreted at the end of 72 h, corresponding 52.6% urinary excretion. The main metabolite in the rat was 2-(2'-methyl-3'-chloro-4'-hydroxy-anilino)-nicotinic acid (72.2%), whereas in the dog it was 2-(2'-methyl-3'-chloro-anilino)-5-hydroxy-nicotinic acid (35.2%).