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• W2051237733 abstract "To measure the oral bioavailability of estetrol (E(4)) in rats relative to its subcutaneous administration and to test the bone-sparing effect of oral E(4) compared to that of ethinylestradiol (EE).In the bioavailability study, E(4) was administered as a single dose of 0.05, 0.5 or 5.0 mg/kg orally or subcutaneously to female rats. Plasma was analyzed using an LC-MS/MS method. The bone study was conducted in 3-month-old female rats assigned to the following seven treatment groups of ten animals each: no treatment; sham-operated + vehicle; bilaterally ovariectomized (OVX) + vehicle; OVX + E(4) 0.1, 0.5, or 2.5 mg/kg/day and OVX + EE 0.1 mg/kg/day. Once-daily treatment by oral gavage was given for 4 weeks and the following measurements were performed: serum osteocalcin, bone mineral density, bone mineral content and bone mineral area of lumbar vertebrae L3-L6, peripheral quantitative computed tomography of the left tibiae and the biomechanical properties of the distal femora.Oral bioavailability of E(4), relative to that of subcutaneous dosing, was 70% and above at the 0.05 and 0.5 mg/kg doses based on the AUC(0-t last). Subcutaneous dosing provided significantly higher E(4) levels at the 1-h time point only, and was comparable to oral dosing after 0.5, 2, 4 and 8 h. In the bone study, E(4) dose-dependently and significantly (1) inhibited the OVX-related increase in osteocalcin levels, (2) increased bone mineral density and content, and (3) increased bone strength, all attenuated by ovariectomy. In this rat model, the relative potency of the highest dose of E(4) (2.5 mg/kg/day) was comparable to the EE dose, used as positive control.Estetrol exhibits high oral bioavailability in the rat, a species considered relevant for pharmacological studies that are predictive for effects on human bone. Oral administration of E(4) conveys dose-dependent bone-sparing effects of high-quality bone in estrogen-depleted OVX rats. Based on its bone-sparing effects, its oral bioavailability and its preclinical safety and efficacy profile, E(4) may be superior to other estrogens and is a potential drug for the prevention of osteoporosis in postmenopausal women." @default.
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• W2051237733 date "2008-01-01" @default.
• W2051237733 modified "2023-10-13" @default.
• W2051237733 title "Oral bioavailability and bone-sparing effects of estetrol in an osteoporosis model" @default.
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• W2051237733 doi "https://doi.org/10.1080/13697130701798692" @default.
• W2051237733 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18464016" @default.
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