Pharmacokinetics and distribution of diphenylhydantoin in kittens

The pharmacokinetics and distribution of 5,5 diphenylhydantoin (DPH) 4 ¹⁴C were studied in kittens after 1 intravenous injection was given at the dose level of 6 mg./kg. Blood concentrations of the drug decreased rapidly during the first 30 minutes after injection, but their subsequent decrease was extremely slow, with an apparent half life of approximately 41.5 hours. The slow decrease in the blood concentrations of 5,5 DPH extrapolated back to an initial blood concentration of 5.3 μg./ml. and a volume of distribution of 1.1 L./kg. Tissue concentrations of DPH decreased over the 1st hour, but were relatively stable thereafter. Concentrations of drug in all tissues studied were higher than those in blood; the concentration in the liver was as much as 3 times that in the blood. The DPH bound reversibly in the tissues, and the maintenance of tissue concentrations was directly related to the blood concentrations of the drug. The prolonged anticonvulsant action of DPH in the cat is due to the long plasma halflife of DPH in this species.