The physiological disposition of  14 C-methsuximide in the rat.
1. (14)C-Methsuximide (N-methyl-(14)C-2-methyl-2-phenylsuccinimide) was rapidly absorbed from the small intestine of the rat (t(1/2) 17.4 min).2. The drug was rapidly and fairly evenly distributed throughout the body with peak blood and tissue levels occurring 1 h after oral administration. At all times, adrenals, body fat, kidneys and liver had higher levels of (14)C-methsuximide than other tissues and the drug freely traversed the blood-brain barrier. However, radioactivity disappeared rapidly from most tissues after the initial phase of the distribution.3. During 24 h, 26% of the orally administered radioactivity was recovered in urine and 29% appeared in expired air as (14)CO(2). The excretion of (14)CO(2) indicated N-demethylation of (14)C-methsuximide to 2-methyl-2-phenylsuccinimide. 2.7% of an administered dose of methsuximide was excreted unchanged in 24 h urine and 2.7% appeared as 2-methyl-2-phenylsuccinimide. 2-Methyl-2-phenylsuccinimide was also detected as a urinary metabolite of methsuximide in man.4. 2-Methyl-2-phenylsuccinimide possesses anticonvulsant activity and it is suggested that this metabolite contributes to the overall anticonvulsant activity and toxicity of methsuximide.5. Rat urine also contained a radioactive substance with similar chromatographic properties to one of the products of alkaline hydrolysis of methsuximide. This compound may arise from the spontaneous decomposition of the parent drug in vivo.
D000273:Adipose Tissue / Q000032:analysis; D000311:Adrenal Glands / Q000032:analysis; D000818:Animals; D000927:Anticonvulsants / Q000032:analysis / Q000097:blood / Q000378:metabolism* / Q000652:urine; D002245:Carbon Dioxide / Q000378:metabolism; D002247:Carbon Isotopes; D006868:Hydrolysis; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000032:analysis; D008099:Liver / Q000032:analysis; D008297:Male; D051381:Rats; D012119:Respiration
D000927:Anticonvulsants; D002247:Carbon Isotopes; D002245:Carbon Dioxide