Toxicokinetics and metabolism of N-[14C]methylpyrrolidone in male Sprague-Dawley rats. A saturable NMP elimination process
Payan, JP; Beydon, D; Fabry, JP; Boudry, I; Cossec, B; Ferrari, E
HERO ID
3539953
Reference Type
Journal Article
Year
2002
Language
English
PMID
| HERO ID | 3539953 |
|---|---|
| In Press | No |
| Year | 2002 |
| Title | Toxicokinetics and metabolism of N-[14C]methylpyrrolidone in male Sprague-Dawley rats. A saturable NMP elimination process |
| Authors | Payan, JP; Beydon, D; Fabry, JP; Boudry, I; Cossec, B; Ferrari, E |
| Journal | Drug Metabolism and Disposition |
| Volume | 30 |
| Issue | 12 |
| Page Numbers | 1418-1424 |
| Abstract | This study evaluated the toxicokinetics of N-[(14)C]methylpyrrolidone ([(14)C]NMP) after intravenous administration (0.1, 1, 10, 100, and 500 mg/kg, in saline solution) or topical application (20 and 40 micro l/cm(2); 10 cm(2), neat) in haired male Sprague-Dawley rats. Whatever the dose, unchanged NMP was intensively distributed into the body with a volume of distribution of 69% of body weight. After this phase, unchanged NMP declined almost linearly with time for 3 to 4 h after administration and then followed a mono-exponential function (t1/2 = 0.8 h) for the three lowest doses. The maximal plasma level of 5-hydroxy-N-methylpyrrolidone (5-HNMP), the main metabolite, was reached 4 to 6 h later for the three lowest doses and 8 to 24 h later for the highest doses. These findings indicate that the elimination of NMP is governed by a saturable metabolism process. The Michaelis-Menten parameters estimated from plasma levels of unchanged NMP were 2 mM and 3.8 mg/h, respectively. Between 4 and 10% of the administered doses were excreted in the urine as unchanged NMP. Urinary clearance of NMP (0.03 to 0.07 ml/min) indicates intensive tubular reabsorption. 5-HNMP was the main urinary metabolite and accounted for 42 to 55% of the administered doses. Its maximal urinary excretion occurred between 4 and 6 h after administration of the three lowest doses and between 8 and 24 h for the two highest doses. Urinary clearance (0.9 to 1.3 ml/min) was compatible with renal elimination by simple glomerular filtration. |
| Doi | 10.1124/dmd.30.12.1418 |
| Pmid | 12433813 |
| Wosid | WOS:000179244200019 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Journal: ISSN: |
| Is Public | Yes |
| Language Text | English |