Pharmacokinetic Studies of 3-Methyl-1-phenyl-2-pyrazolin-5-one (MCI-186) in Dogs: Blood or Plasma Levels, Metabolism and Excretion after a Single Intravenous Administration

Abstract

Blood or plasma levels, metabolism and excretion were investigated after a single intravenous administration of ¹⁴C-MCI-186 (2 mg/kg) to male dogs.
1) Decrease of radioactivity from whole blood was more delayed than from plasma, and transfer rates to blood cells increased parallel with the course of time.
2) Unchanged MCI-186 in plasma decreased rapidly with the half-lives of 0.07 hr (t_1/2α) and 0.70 hr (t_1/2β). Areas under the concentration time curves (AUC_0→∞) of unchanged MCI-186, sulfate and glucuronide of MCI-186 in plasma consisted 5.2%, 61.1% 16.2% of the AUC_0→∞ of the radioactivity in plasma, respectively.
3) The dosed radioactivity was excreted to urine and feces until 120 hr after administration, in 84.1% and 13.2%, respectively, and main excretion route of MCI-186 was urinary excretion in dogs. 2.8%, 66.2% and 9.4% of the dosed radioactivity were excreted to urine as the forms of unchanged MCI-186, sulfate and glucuronide of MCI-186, respectively.
4) In dogs, the clearanc e of unchanged MCI-186 and percentages of MCI-186 sulfate to total radioactivity in plasma and urine were higher than those in rats. And unknown metabolites observed in dogs, accounted for a small fraction.