Rapid microbial degradation of organic nitrates in rat excreta. Re-examination of the urinary and fecal metabolite profiles of pentaerythritol tetranitrate in the rat

Abstract

The in vitro stabilities of three organic nitrates, viz. pentaerythritol tetranitrate ( PETN ), nitroglycerin (NTG), and isosorbide dinitrate (ISDN) in rat urine, and of PETN in rat feces were examined. PETN , NTG, and ISDN degraded completely in rat urine following incubation for 24 hr at either 25 or 37 degrees C. Degradation of PETN , NTG, and ISDN was absent in sterilized urine under the same conditions. These data suggested that decomposition of organic nitrates in untreated urine was usually rapid and extensive, and was primarily of microbial origin. Stability of these organic nitrates could also be maintained when urine samples were stored in packed ice. Rapid and extensive microbial degradation of PETN was also found in rat fecal homogenates, suggesting the possibility of organic nitrate metabolism by intestinal microflora. The metabolic profiles of PETN in rat urine and feces following intra-arterial and oral dosing of this organic nitrate were then re-examined. The data confirmed a previous finding that in vivo PETN excretion in urine was minimal. However, contrary to data which showed about 8% fecal recovery after oral dosing, our results suggested a smaller (2%) fecal PETN recovery with oral dosing. It appeared likely then that unabsorbed PETN might be further metabolized by gut flora.