Fructose-1,6-diphosphate (FDP), a glycolytic metabolite, has been reported to protect susceptible organs during hypoxia or ischemia. However, there is paucity of human data on its pharmacokinetics a er being exogenously administered. In the current study, the preliminary pharmacokinetics of FDP given orally to humans was investigated, and no typical peak was observed in the serum drug-time curve. Then, the pharmacokinetic studies were performed following multiple doses of FDP in rats, and the Caco-2 monolayer model was used to study the absorption of FDP in vitro. The results suggested that plasma FDP concentration was signifi cantly increased a er oral multiple doses of 180 mg kg -1 but not 90 mg kg -1 of FDP, and FDP was partly depleted during the absorption, which was supposed to be consumed by the intestinal epithelium cells. Thus, we conclude that a high dose of FDP should be orally administered in order to get an eff ective plasma level.Keywords: fructose-1,6-diphosphate, ischemia, hypoxia, pharmacokineticsFructose-1,6-diphosphate (FDP) is an endogenous intermediate metabolite of glucose. Most of glucose and fructose is converted to FDP when entering a cell. It has been increasingly recognized that FDP can protect ischemic or hypoxic tissue a er acute ischemia, although the mechanisms have not been fully clarifi ed yet.Previous studies suggested that exogenous FDP could augment the anaerobic carbohydrate utilization and improve the cellular energy metabolism in ischemic and hypoperfused tissues. Hypoxia forces ischemic tissue to anaerobic glycolysis for energy, which yields two molecules of ATP per glucose in contrast to 36 molecules of ATP generated during oxidative phosphorylation (1). Addition of exogenous FDP can produce two more molecules of ATP in an uncompensated anaerobic environment and hence facilitate the recovery of ischemia tissue. FDP breaks down into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate, which will further break down into two molecules of pyruvate and fi nally produce two molecules of ATP (Fig. 1).