Betaine is catabolized mainly in the mitochondria of liver and kidney cells. The transmethylation of betaine via betaine homocysteine methyl transferase (BHMT) leads to the formation of dimethylglycine.
Betaine is absorbed from the small intestines into the enterocytes. It is released by the enterocytes into the portal circulation which carries it to the liver where there is significant first-pass extraction and first-pass metabolism of betaine. The principal metabolic reaction is the transfer of a methyl group from betaine to homocysteine via the enzyme betaine-homocysteine methyltransferase. The products of the reaction are L-methionine and dimethylglycine. Betaine hydrochloride is converted to betaine in the alkaline environment of the small intestine.
In small, open label trials of betaine therapy for homocystinuria as well as in small controlled trials of betaine in other conditions (Alzheimer disease, nonalcoholic steatohepatitis), serum enzyme elevations and clinically apparent liver injury were not reported. Indeed, in some studies, betaine has been associated with significant declines in preexisting serum enzyme elevations in a proportion of patients with nonalcoholic fatty liver disease.
参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 用于研究药物诱导肝损伤的FDA批准药物标签，药物发现今日，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按在人类中发展药物诱导肝损伤风险排名的最大参考药物清单。药物发现今日2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
Betaine is rapidly absorbed and distributed. In healthy volunteers (n=12) given 50 mg/kg of betaine, the Cmax, tmax and AUC0,∞ were 0.939 mmol/L, 0.90 h and 5.52 mmol⋅h/L, respectively. No significant changes in absorption kinetics were observed after repeated betaine administration (100 mg/kg/day for 5 days). The absolute bioavailability of betaine anhydrous has not been determined.
Betaine is mainly eliminated by metabolism. With a slow elimination rate and assuming 100% bioavailability, the renal clearance of betaine is negligible (5% of total body clearance).
来源:DrugBank
吸收、分配和排泄
分布容积
根据对健康志愿者（n=12）进行的50毫克/公斤甜菜碱的研究，分布体积为1.3升/公斤。
Based on a study done on healthy volunteers (n=12) given 50 mg/kg of betaine, the volume of distribution was 1.3 L/kg.
Betaine is absorbed from the small intestines into the enterocytes. It is released by the enterocytes into the portal circulation which carries it to the liver where there is significant first-pass extraction and first-pass metabolism of betaine. The principal metabolic reaction is the transfer of a methyl group from betaine to homocysteine via the enzyme betaine-homocysteine methyltransferase. The products of the reaction are L-methionine and dimethylglycine. Betaine hydrochloride is converted to betaine in the alkaline environment of the small intestine.
[EN] A CONJUGATE OF A TUBULYSIN ANALOG WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN ANALOGUE DE TUBULYSINE AVEC DES LIEURS RAMIFIÉS
申请人：HANGZHOU DAC BIOTECH CO LTD
公开号：WO2019127607A1
公开（公告）日：2019-07-04
The present invention relates to the conjugation of a tubulysin analog compound to a cell-binding molecule with branched/side-chain linkers for having better delivery of the conjugate compound and targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of a tubulysin analog molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and autoimmune disease.
The invention provides novel imidazopyrazine derivatives having the general formula (I), wherein Rx and R3 to R5 are as described herein (formula (I)) or pharmaceutically acceptable salts thereof. Further provided are pharmaceutical compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds as medicaments, in particular methods of using the compounds as antibiotics for the treatment or prevention of bacterial infections and resulting diseases.
Chloral Hydrate Polymorphs and Cocrystal Revisited: Solving Two Pharmaceutical Cold Cases
作者：Daniel O’ Nolan、Miranda L. Perry、Michael J. Zaworotko
DOI：10.1021/acs.cgd.6b00032
日期：2016.4.6
crystal structures of the β-form of chloralhydrate and its pharmaceutical cocrystal with betaine have not yet been reported. In this contribution, the single crystal structures and physical properties of these crystal forms are reported for the first time. The previously termed “high temperature” β-form of chloralhydrate was obtained by melting the α-form of chloralhydrate and crystallizing from the melt
Rate and equilibrium studies of the reaction of oxyanions with 2-phenyloxazol-5(4H)-one
作者：Edwin Chrystiuk、Adelina Jusoh、Dino Santafianos、Andrew Williams
DOI：10.1039/p29860000163
日期：——
Equilibrium constants for the reaction of phenoxide ions with 2-phenyloxazol-5(4H)-one at 25 °C and 1 M ionic strength obey a Brønsted relationship (log kOH/kArO= log K′=–1.73pKArOH– 15.81) and are not subject to steric effects from ortho-substituents. Both forward and reverse rate parameters exhibit steric effects, and the Brønsted equations for meta- and para-substituted species are log kOH=–0.81
在25°C和1 M离子强度下，酚盐离子与2-苯基恶唑-5（4 H）-one反应的平衡常数服从布朗斯台德关系（log k OH / k ArO = log K '= –1.73p K ArOH – 15.81），并且不受邻位取代基的空间位阻的影响。正向和反向速率参数均显示出空间效应，间位和对位取代物种的Brønsted方程为log k OH = –0.81 p K ArOH + 9.75，log k ArO = 0.95p KArOH – 6.40。在p K ArOH 5-11的区域内，Brønsted线没有中断，这与一个过渡态一致。低碱度的氧阴离子存在向上偏差（p K XOH <5）；这些氧阴离子之一，甜菜碱，由于其与恶唑酮的反应大于2，具有溶剂性氘氧化同位素作用，这与攻击这些物质的一般基本机理相符。酚酸根阴离子的亲核攻击结果与羰基的协同位移一致。
Bimolecular Electron and Energy Transfer Reactivity of Exchange-Coupled Dinuclear Iron(III) Complexes
作者：Brandon T. Weldon、Daniel E. Wheeler、James P. Kirby、James K. McCusker
DOI：10.1021/ic010659l
日期：2001.12.1
experimentally establish a link between Heisenberg spin exchange and chemical reactivity. The acceptors are members of the oxo/hydroxo-biscarboxylato class of dinuclear Fe(III) compounds, where protonation of the oxo bridge provides a means for modulating the magnitude of spin exchange within the cluster. Photoexcitation of solutions containing Ru(II) polypyridyl sensitizers and the Fe(III) complexes results in
