Preparation of 3-deoxy-3-deuteroestrone and 3-deoxy-4-14C-estrone.
3-Deoxy-3-deuteroestrone (1,3,5(10)-estratrien-17-one-3-d) and 3-deoxy-4-14C-estrone (1 ,3 ,5(10)-estratrien-17-one-14C) have been prepared. The mechanism of reductive dehalogenation of aryl iodides with lithium aluminum deuteride is discussed. The 13C-NMR spectrum of 3-deoxy-3-deuteroestrone is discussed.
4-Hydroxyestrone: A new metabolite of estradiol-17β from humans
Abstract 4-Hydroxyestrone has been identified, by reverse isotope dilution, as a urinary metabolite after injection of a mixture of 4- 3 H- and 4- 14 C-estradiol-17β into a 23 year old woman and a 39 year old man. This new metabolite accounted for 1.1% of the - 14 C dose administered to the woman and 0.51% of the - 14 C dose administered to the man. 7.3% Of the 3 H dose was liberated into the body water pool of the woman and 6.1% into that of the man. The yields of radioactive estrone, estradiol-17β, estriol, 2-hydroxyestrone, 2-methoxyestrone and 2-hydroxyestrone 3-methyl ether were also measured in both the Ketodase and Glusulase hydrolyzed urinary fractions from both subjects.
Pharmacokinetics and Metabolism of 14C-Brivaracetam, a Novel SV2A Ligand, in Healthy Subjects
This study was designed to investigate the human absorption, disposition, and mass balance of 14C-brivaracetam, a novel high affinity SV2A ligand with potent anticonvulsant activity. Six healthy male subjects received a single p.o. dose of 14C-brivaracetam (150 mg, 82 μCi, or 3.03 MBq). Serial blood and complete urine and feces were collected until 144 h postdose. Expired air samples were obtained until 24 h. Brivaracetam was rapidly absorbed, with Cmax of 4 μg/ml occurring within 1.5 h of dosing. Unchanged brivaracetam amounted to 90% of the total plasma radioactivity, suggesting a modest first-pass effect. Plasma protein binding of radioactivity was low (17.5%). Urinary excretion exceeded 90% after 2 days, and the final mass balance reached 96.8% of the radioactivity in urine and 0.7% in feces. Only 8.6% of the radioactive dose was recovered in urine as unchanged brivaracetam, the remainder being identified as non–cytochrome P450 (P450)- and P450-dependent biotransformation products resulting from hydrolysis of the amide moiety (M9, 34.2%), hydroxylation of the n-propyl side chain (M1b, 15.9%), and a combination of these two pathways leading to the hydroxy acid (M4b, 15.2%). Minor amounts of taurine and glucuronic acid conjugates and other oxidized derivatives were also identified. Brivaracetam is completely absorbed, is weakly bound to plasma proteins, extensively biotransformed through several metabolic pathways, and eliminated renally.