STUDIES ON THE GASTROINTESTINAL ABSORPTION OF PHOSPHOCITRATE, A POWERFUL CONTROLLER OF HYDROXYAPATITE FORMATION

In situ gastrointestinal perfusion and a chemical induced subcutaneous calcergy model were used to examine the oral bioavailability of the p otent calcification inhibitor, phosphocitrate (PC). Formation of calce rgic plaques was observed to decrease by approx. 34% when 450 mg PC/kg body weight per day was given to rats by gavage. An equivalent respon se was observed when only 10 mg PC/kg per day was given intraperitonea lly thus indicating reduced bioavailability of the compound by the ora l route. Luminal metabolism of PC did not contribute significantly to its overall poor oral bioavailability. Data derived from perfusion of in situ isolated intestinal segments with PC concentrations from 5 to 20 mM indicated luminal absorption by a passive transport process. Stu dies with radiolabeled PC confirmed the presence of small amounts of [ C-14]PC and [C-14]citrate in portal blood. It was concluded that the membrane transport characteristics for PC were limiting transfer and t hat a possible future improvement might arise through the incorporatio n of a lipophilic moiety into the molecule.