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Abstract

Biotransformation of organic nitrate esters in vitro by human liver, kidney, intestine, and blood serum.

F A Posadas del Rio, F Jaramillo Juárez and R Camacho García
Drug Metabolism and Disposition May 1988, 16 (3) 477-481;
F A Posadas del Rio
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F Jaramillo Juárez
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R Camacho García
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Abstract

The biotransformation of glycerol trinitrate (GTN), isosorbide dinitrate (ISD), pentaerythritol tetranitrate (PETN), erythritol tetranitrate (ETN), and mannitol hexanitrate (MHN) by extracts from human liver, small intestine mucosa, kidney, and blood serum was investigated. The glutathione-dependent organic nitrate ester reductase activity of the intestinal mucosa was 21, 4, 4, and 2 times higher than the liver activity for ISD, PETN, GTN, and ETN, respectively. The liver enzymatic activity for MHN was 35% higher than the intestinal activity and 56% higher than kidney enzyme activity. The order of increasing enzymatic rates was: ISD = PETN less than GTN less than ETN less than MHN in the intestinal mucosa; ISD less than PETN less than GTN less than ETN less than MHN in the liver; and ISD less than PETN = GTN less than ETN less than MHN in the kidney. Human serum also metabolized these organic nitrates at lower rates than the studied organs. Thus, the serum specific activities were 1/5 for MHN, 1/30 for ETN, 1/40 for GTN, 1/44 for ISD, and 1/2000 for PETN of the activity present in kidney. On the other hand, the activity of human albumin was lower than that of blood serum. The serum and albumin activities were not modified by reduced glutathione or sulfhydryl inhibitors. These results suggest that small intestine may play an important role in the biotransformation of these drugs at their absorption site, after oral administration. They also demonstrate the possible participation of various human tissues in the overall metabolism of organic nitrate esters.

 

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Drug Metabolism and Disposition
Vol. 16, Issue 3
1 May 1988
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Abstract

Biotransformation of organic nitrate esters in vitro by human liver, kidney, intestine, and blood serum.

F A Posadas del Rio, F Jaramillo Juárez and R Camacho García
Drug Metabolism and Disposition May 1, 1988, 16 (3) 477-481;

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Abstract

Biotransformation of organic nitrate esters in vitro by human liver, kidney, intestine, and blood serum.

F A Posadas del Rio, F Jaramillo Juárez and R Camacho García
Drug Metabolism and Disposition May 1, 1988, 16 (3) 477-481;
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