title: Synthesis and pharmacokinetics of strontium fructose 1,6-diphosphate (Sr-FDP) as a potential anti-osteoporosis agent in intact and ovariectomized rats.
abstract: 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 440mg/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)<1h 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 6h, and the level of Sr decreased close to the baseline in heart, liver, spleen, lung, intestine, brain and kidney after 12h. The cumulative amounts of Sr over 96h 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.
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Guanji
authors.initials: G
authors.lastname: Wang
authors.forename: Zimei
authors.initials: Z
authors.lastname: Wu
authors.forename: John P
authors.initials: JP
authors.lastname: Shaw
authors.forename: Yinying
authors.initials: Y
authors.lastname: Hu
authors.forename: Yubin
authors.initials: Y
authors.lastname: Wang
authors.forename: Yaya
authors.initials: Y
authors.lastname: Zheng
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Yang
authors.forename: Hanjie
authors.initials: H
authors.lastname: Ying
mesh_terms: D000818:Animals; D005260:Female; D005635:Fructosediphosphates / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D023421:Models, Animal; D010024:Osteoporosis / Q000188:drug therapy*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013324:Strontium / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D005635:Fructosediphosphates; C029063:fructose-1,6-diphosphate; D013324:Strontium