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Research ArticleArticle

THE EXCRETION AND DISTRIBUTION OF MEPROBAMATE AND ITS METABOLITES

Sidney S. Walkenstein, Cornelius M. Knebel, Joyce A. MacMullen and Joseph Seifter
Journal of Pharmacology and Experimental Therapeutics August 1958, 123 (4) 254-258;
Sidney S. Walkenstein
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Cornelius M. Knebel
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Joyce A. MacMullen
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Joseph Seifter
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Abstract

The absorption, excretion, distribution and metabolism of C14-labeled meprobamate, labeled in both carbamate groups, following oral and intraabdominal injection was studied in rats and dogs and of the nonlabeled drug after oral administration to humans. The drug was found to be readily absorbed from the gastrointestinal tract. Significant amounts of C14 began to appear in tile Urine within 30 minutes after an oral or intra-abdominal dose and by 24 hours most had been excreted. Feces contained less than 10 per cent of the dose. Blood levels of C14 reached a peak two hours after oral administration; 50 per cent of the amount present was unchanged meprobarnate. After adnlinistration of the drug to rats, lung, kidney and liver were found to have the highest levels of radioactivity.

The major metabolite, accounting for approximately 60 per cent of the dose in dogs, was isolated and identified as hydroxymeprobamate (2 - hydroxyrnethyl - 2 - n -propyl - 1 ,3 - propanediol dicarbamate). When this compound or the corresponding tricarbamate was administered to dogs no nleprobamate-like activity was observed.

A specific colorimetric method for determination of meprobarnate in plasma and urine based on the Brown modification of the Kober reaction was developed and is sensitive to concentrations as low as 5 microgm. per ml.

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    • Received May 5, 1958.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 123, Issue 4
1 Aug 1958
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Research ArticleArticle

THE EXCRETION AND DISTRIBUTION OF MEPROBAMATE AND ITS METABOLITES

Sidney S. Walkenstein, Cornelius M. Knebel, Joyce A. MacMullen and Joseph Seifter
Journal of Pharmacology and Experimental Therapeutics August 1, 1958, 123 (4) 254-258;

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Research ArticleArticle

THE EXCRETION AND DISTRIBUTION OF MEPROBAMATE AND ITS METABOLITES

Sidney S. Walkenstein, Cornelius M. Knebel, Joyce A. MacMullen and Joseph Seifter
Journal of Pharmacology and Experimental Therapeutics August 1, 1958, 123 (4) 254-258;
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