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141.
Lønning PE Geisler J Johannessen DC Gschwind HP Waldmeier F Schneider W Galli B Winkler T Blum W Kriemler HP Miller WR Faigle JW 《The Journal of steroid biochemistry and molecular biology》2001,77(1):39-47
Formestane (Lentaron(R), 4-hydroxyandrostenedione) is a steroidal aromatase inhibitor used for treatment of advanced breast cancer. Clinically, it is administered as a depot form once fortnightly by intramuscular (i.m.) injection. To investigate the pharmacokinetics, bioavailability and metabolism of the drug, seven patients received single 250 mg i.m. doses of commercial formestane on Days 0, 21, 35, 49 and 63 of this trial. On Day 63, three of the patients received an additional single intravenous (i.v.) pulse dose of 1 mg of 14C-labelled formestane. The plasma kinetics after i.m. dosing confirmed a sustained release of formestane from the site of injection. Within 24-48 h of the first dose, the circulating drug reached a C(max) of 48.0+/-20.9 nmol/l (mean+/-S.D.; N=7). At the end of the dosing interval, after 14 days, the plasma concentration was still at 2.3+/-1.8 nmol/l. The kinetic variables did not significantly change during prolonged treatment. Intramuscular doses appear to be fully bioavailable. Following i.v. injection of 14C-formestane, the unchanged drug disappeared rapidly from plasma, the terminal elimination half-life being 18+/-2 min (N=3). Plasma clearance, CL was 4.2+/-1.3 l/(h kg) and the terminal distribution volume V(z) was 1.8+/-0.5 l/kg. The drug is mainly eliminated by metabolism, renal excretion of metabolites accounting for 95% of dose. The excretory balance of 14C-compounds in urine and faeces totals up to 98.9+/-0.8% of the i.v. dose after 168 h. The 14C-compounds in plasma and urine were separated by HPLC, and three major metabolites were submitted to structural analysis by MS, NMR and UV spectroscopy. One of the metabolites is the direct 4-O-glucuronide of formestane. The other two represent 3-O-sulfates of the exocons 3beta,4beta-dihydroxy-5alpha-androstane-17-one and 3alpha,4beta-dihydroxy-5alpha-androstane-17-one, their ratio being 7:3. These exocons are formed by stereoselective 3-keto reduction, accompanied by reduction of the 4,5-enol function. The exocons do not inhibit human placental aromatase activity in vitro. 相似文献
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The infrared spectrum and water binding of collagen as a function of relative humidity 总被引:1,自引:0,他引:1
The infrared spectra of undenatured bovine tendon collagen were investigated at 25°C and relative humidities from 0 to 95%. Suitable samples were prepared by forcing frozen suspensions of the material in distilled water through a stainless steel capillary. The samples were investigated by electron microscopy before and after the spectra were obtained to ascertain that no denaturation had taken place while the sample was exposed to infrared radiation. Temperature controlled absorption cells were constructed which permitted the passing of air with a known water content over the sample film. Gradual changes were observed in the frequencies and intensities of characteristic amide bands over the relative humidity range of 0 to 75%. These changes are particularly pronounced for the amide II band, associated with bending motions of peptide NH bonds. They lead to the conclusion that water molecules are gradually attached to peptide NH bonds within the triple helix over a wide range of relative humidity. Changes in CH deformation bands suggest that CH to O hydrogen bonding does occur and that it is more pronounced in collagen exposed to high relative humidity. 相似文献
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Summary Identical twins with symptoms very similar to the HMC syndrome are described. 相似文献
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