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During and after a single or repeated intravenous administration of 14C-MCI-186 (2 mg/kg/day) for 7, 14 and 21 days to male rats, blood and plasma levels, distribution, metabolism, excretion and accumulation of MCI-186 were investigated. 1) Tissue levels of radioactivity at 5 min after each dosing during repeated administration were constant except in the blood vessel (aorta). Tissue levels of radioactivity at 24 hr increased to 2 ?? 9 times by 21 days repeated administration, but they were saturated after 7 or 14 days repeated administration. Transfer rates to blood cells also increased by repeated administration. Decrease of radioactivity from tissues was delayed after 21 days repeated administration, especially from the blood vessel (aorta). 2) Concentrations of the unchanged MCI-186 and metabolites in plasma, brain, liver and kidney at 5 min after each dosing during repeated administration were not significantly changed by repeated administration, however concentrations of the unchanged MCI-186 in the liver showed a tendency to decrease by repeated administration. 3) During 21 days repeated administration, radioactivities were excreted to urine and feces constantly, and until 192 hr after final dosing of repeated administration, 88% and 10% of the total dose were excreted to urine and feces, respectively. Total excretion extent reached 99% of the dose, therefore remaining fraction in the rat body was suggested to be minimal. Urinary excretion of the unchanged MCI-186 and metabolites were also not affected by repeated administration, except the excretion rates of MCI-186 glucuronide those seemed to decrease by repeated administration.

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Pharmacokinetic Studies of 3-Methyl-1-phenyl-2-pyrazolin-5-one(MCI-186) in rats. (2). Blood and Plasma Levels, Distribution, Metabolism, Excretion and Accumulation during and after Repeated Intravenous Administration.