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Research ArticleArticle

CLEARANCE AND METABOLISM OF ORGANIC NITRATES

EUGENE M. JOHNSON JR., ANNE B. HARKEY, DELORES J. BLEHM and PHILIP NEEDLEMAN
Journal of Pharmacology and Experimental Therapeutics July 1972, 182 (1) 56-62;
EUGENE M. JOHNSON JR.
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ANNE B. HARKEY
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DELORES J. BLEHM
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PHILIP NEEDLEMAN
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Abstract

The rate of degradation of several organic nitrates by isolated perfused rat liver was compared to the rates of metabolism in vivo. The disappearance of erythrityl tetranitrate (T1/2, one minute) indicated essentially complete removal in each pass through the liver. The half times of glyceryl trinitrate (two minutes), isosorbide dinitrate (five minutes) and pentaerythritol trinitrate (seven minutes) were longer. The observed in vivo half times of isosorbide dinitrate and glyceryl trinitrate were one minute each whereas the half-time of mannitol hexanitrate was approximately 10 seconds. The disappearance of parent compound correlated with a rapid rise in blood levels of metabolites. Rat blood in vitro metabolized mannitol hexanitrate rapidly (T1/2, one mintue), but glyceryl trinitrate and isosorbide dinitrate were metabolized much more slowly (T1/2, 15-20 minutes). It is concluded that the rapid in vivo disappearance of organic nitrates represents the sum of distribution, nonhepatic metabolism (mannitol hexanitrate) and hepatic metabolism which is limited only by the rate at which the drug is presented to the liver via the blood.

Footnotes

    • Received July 9, 1971.
    • Accepted March 13, 1972.
  • © 1972, by The Williams & Wilkins Company

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Journal of Pharmacology and Experimental Therapeutics
Vol. 182, Issue 1
1 Jul 1972
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Research ArticleArticle

CLEARANCE AND METABOLISM OF ORGANIC NITRATES

EUGENE M. JOHNSON, ANNE B. HARKEY, DELORES J. BLEHM and PHILIP NEEDLEMAN
Journal of Pharmacology and Experimental Therapeutics July 1, 1972, 182 (1) 56-62;

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Research ArticleArticle

CLEARANCE AND METABOLISM OF ORGANIC NITRATES

EUGENE M. JOHNSON, ANNE B. HARKEY, DELORES J. BLEHM and PHILIP NEEDLEMAN
Journal of Pharmacology and Experimental Therapeutics July 1, 1972, 182 (1) 56-62;
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