Synthesis and pharmacokinetics of strontium fructose 1,6-diphosphate (Sr-FDP) as a potential anti-osteoporosis agent in intact and ovariectomized rats

摘要

A novel strontium compound has been synthesized by the reaction of fructose-1,6-diphosphate with strontium (Sr-FDP). The compound was characterized and confirmed with elemental analyses and spectroscopic (IR, NMR) methods. The pharmacokinetic profiles of Sr-FDP were investigated in Sprague-Dawley rats following oral administration at a dose of 110, 220, and 440 mg/kg respectively. Pharmacokinetic differences were also compared in intact rats and ovariectomized rats with and without estrogen supplement. Strontium concentrations in plasma, urine, tissue and feces were determined by graphite furnace atomic absorption spectroscopy (GFAAS). The results showed that Sr-FDP was absorbed rapidly with T_(max) < 1 h in all the groups with AUC_(0-∞) proportional to the oral dose. The pharmacokinetic profiles were characterized by long half-life, a large apparent volume of distribution. The highest Sr concentration was observed in the bone at 6 h, and the level of Sr decreased close to the baseline in heart, liver, spleen, lung, intestine, brain and kidney after 12 h. The cumulative amounts of Sr over 96 h were found to be ～3% in urine, but ~ 70% in feces suggesting that the parent drug was mainly excreted from the intestine. The C_(max) and AUC _(0-∞) of Sr-FDP in ovariectomized rats were significantly decreased compared to those in intact rats, and this trend was ameliorated by using 17-beta-estradiol (E_2) treatment in the ovariectomized rats.