Disposition and metabolism of double-labeled [3H and 14C] N-methyl-2-pyrrolidinone in the rat.
The disposition of N-methyl-2-pyrrolidinone (NMP) was studied in the rat using tritium-labeled ([4-3H]NMP) and carbon-14-labeled ([methyl-14C]NMP and [ring-14C]NMP) radioisomers. Male Sprague-Dawley rats were administered a single intravenous dose (45 mg/kg) of 5.0 microCi of 3H or 14C for single-labeled disposition studies or 5.0 microCi of 3H and 2.5 microCi of 14C for double-labeled studies (2:1 ratio, 3H:14C). Plasma levels of intact NMP were analyzed by HPLC through 6 hr after dosing and suggested a rapid distribution phase followed by a slow elimination phase. The half-life for the terminal elimination phase from plasma was about 7 hr for both 14C-isomers and 9.9 hr for the 3H-isomer. The major route of excretion of radioactivity was via the urine and accounted for about 70% of the dose within 12 hr. After 24 hr, cumulative excretion in urine represented about 80% of the dose. The 2:1 ratio of administered 3H:14C was maintained in urine through 6 hr. Measurement of radioactivity in tissues at 6 hr showed the liver and intestines to contain the highest accumulations of radioactivity, representing approximately 2% and 3% of the dose, respectively. Tissue distribution of radioactivity was similar for all three radiolabeled isomers and showed that NMP was extensively distributed to all major organs. Radiomonitored HPLC analyses of urine revealed the presence of one major and two minor metabolites. The major metabolite, representing 70-75% of the administered dose of radioactivity, was found to retain all three radiolabeled positions.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001646:Bile / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D007553:Isotope Labeling; D008297:Male; D011760:Pyrrolidinones / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012997:Solvents / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D011760:Pyrrolidinones; D012997:Solvents; C038678:N-methylpyrrolidone