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Abstract

Plasma elimination and urinary excretion of methapyrilene in the rat.

D W Kelly, C L Holder, W A Korfmacher and W Slikker Jr
Drug Metabolism and Disposition November 1990, 18 (6) 1018-1024;
D W Kelly
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C L Holder
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W A Korfmacher
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W Slikker Jr
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Abstract

The metabolism and elimination of methapyrilene (2-[(2-dimethylaminoethyl)-2-thenylamino]pyridine) were characterized after the iv administration of 0.7 mg/kg or 3.5 mg/kg methapyrilene HCl plus [14C]methapyrilene HCl to adult male Fischer-344 rats. Approximately 40% and 35% of the administered dose was excreted in the urine in the first 24 hr in the low and high dose groups, respectively, as determined by liquid scintillation spectrophotometry. Fecal excretion accounted for 38% and 44% of the administered dose in the first 24 hr in the low and high dose groups, respectively, as confirmed via combustion analysis. The 24-hr urinary metabolic products consisted of one major and five minor radiolabeled compounds. The major metabolite was isolated with reversed-phase HPLC and identified as methapyrilene N-oxide. This was accomplished by comparison of the chromatographic and mass spectral characteristics of this metabolite with that of authentic methapyrilene N-oxide. Methapyrilene and mono-N-desmethyl methapyrilene also were identified after isolation with reversed-phase HPLC and comparison of their mass spectral and/or chromatographic properties with those of authentic compounds. The plasma metabolic profile was essentially the same as the urinary profile. The elimination of methapyrilene from plasma occurred through a first-order process. The terminal plasma elimination t1/2 of methapyrilene did not increase with increasing doses (2.75 hr, 0.7 mg/kg; 2.81 hr, 3.5 mg/kg); thus, methapyrilene does not exhibit dose-dependent elimination over this 5-fold dose range.

 

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Drug Metabolism and Disposition
Vol. 18, Issue 6
1 Nov 1990
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Abstract

Plasma elimination and urinary excretion of methapyrilene in the rat.

D W Kelly, C L Holder, W A Korfmacher and W Slikker
Drug Metabolism and Disposition November 1, 1990, 18 (6) 1018-1024;

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Abstract

Plasma elimination and urinary excretion of methapyrilene in the rat.

D W Kelly, C L Holder, W A Korfmacher and W Slikker
Drug Metabolism and Disposition November 1, 1990, 18 (6) 1018-1024;
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