Pharmacokinetics of nitrate in humans: role of gastrointestinal absorption and metabolism.

A model to describe the response of the blood pool to an oral dose of nitrate in humans has been developed. The permeability-area product of the small intestine to nitrate was estimated by comparing simulations from a three-compartment model with published data for blood nitrate concentration following nitrate ingestion. The transport of nitrate from the bloodstream to the lumen of the large intestine and the metabolism of nitrate by enteric bacteria were examined by including an additional compartment representing the large bowel. The simulations indicate that the bacteria of the large intestine may be responsible for about half of the extrarenal removal of nitrate from the body. This prediction was tested experimentally by comparing the urinary recoveries of 15NO3- in conventional and germfree rats following an i.p. dose of Na15NO3. The mean urinary recovery in germfree rats (71% of dose) substantially exceeded that in rats with conventional bacterial flora (54%). This suggests that of the 40-45% of a nitrate dose that is metabolized in the body rather than excreted in urine as nitrate, approximately half is metabolized by mammalian processes and approximately half by enteric bacteria. This conclusion is consistent with that obtained from our pharmacokinetic model of nitrate in humans.