Disposition of ipriflavone (TC-80) in rats and dogs.

Abstract

Oral 14C-ipriflavone was absorbed by rats to give a maximum plasma 14C level at 1.5h and a half-life of 5.8h. In dogs, after po dosing, the plasma 14C peaked at 0.5h, followed by gradual decline. The plasma of both animals contained mostly metabolites, with small amounts of unchanged Ipriflavone. In rats, 14C was distributed widely in tissues, with relatively high concns. in the liver, kidney and gut. Distribution in rat thigh bone of unmetabolized ipriflavone was also demonstrated. 14C-Ipriflavone was eliminated mostly as metabolites within 48 and 72h, respectively, in rats and dogs. Rats excreted more 14C in urine than in feces, whereas the reverse was noted in dogs. Biliary excretion and reabsorption of 14C were also obvious in both animals.

TAK‐778 enhances osteoblast differentiation of human bone marrow cells

“…The results showed that TAK-778 stimulates expression of markers characteristic of the osteoblast phenotype in human bone marrow cells, which are, ALP activity and bone-like formation in a time and dose-dependent way. The in vitro concentrations of TAK-778 used in this work correspond to plasma concentrations of ipriflavone, a precursor of TAK-778, reached when it is orally administered at therapeutic doses [Yoshida et al, 1989]. Moreover, in vitro activity of TAK-778 has been reported at concentrations of 10 À6 M or higher in rat bone marrow cells .…”

Cross-species and interassay comparisons of phytoestrogen action.

“…These doses produce plasma concentrations (135) similar to the in vitro concentrations (≥ 100 nM) required for inhibition of osteoclast differentiation (136) and bone resorption (137). Much higher oral doses (50-400 mg/kg/day) of IPR have been required to prevent bone loss in ovariectomized rats (138), doses that also produce plasma concentrations similar to the effective in vitro concentrations (139,140). COM also inhibits bone resorption in vitro (141) and is a more potent agent, preventing bone loss at oral doses of 1-2 mg/kg/day (142,143).…”

Isoflavones, lignans and stilbenes - origins, metabolism and potential importance to human health

“…In a carefully controlled dietary intervention study, only between 2 and 13% of the daily dose (45 mg total isoflavone) was recovered in urine,81 while Xu et al 84 reported average urinary recovery of daidzein and genistein to be 21% and 9% respectively, irrespective of the dose given (0.7, 1.3, 2.0 mg isoflavone kg −1 body weight, fed as soya milk). In healthy male volunteers, 40–50% of an ingested dose of 200 mg ipriflavone (an isoflavone derivative) was absorbed,85 while in dogs, approximately 24% of an oral dose of [ 14 C]‐ipriflavone (20 mg kg −1 body weight) was absorbed 86. It is evident from the comparisons between rats and dogs86 that there are both similarities and differences between species in their metabolism of isoflavones, and it is not clear which, if either, humans resemble.…”

“…In healthy male volunteers, 40–50% of an ingested dose of 200 mg ipriflavone (an isoflavone derivative) was absorbed,85 while in dogs, approximately 24% of an oral dose of [ 14 C]‐ipriflavone (20 mg kg −1 body weight) was absorbed 86. It is evident from the comparisons between rats and dogs86 that there are both similarities and differences between species in their metabolism of isoflavones, and it is not clear which, if either, humans resemble. However, based on the corresponding plasma genistein concentrations in rats and humans,84, 87 rats provide a useful model for investigation of the metabolic fate of these compounds.…”