Following oral dosing, MPA is extensively metabolized in the liver via hydroxylation, with subsequent conjugation and elimination in the urine. ...MPA is almost exclusively eliminated via hepatic metabolism. In 14 patients with advanced liver disease, MPA disposition was significantly altered (reduced elimination). In patients with fatty liver, the mean percent dose excreted in the 24-hour urine as intact MPA after a 10 mg or 100 mg dose was 7.3% and 6.4%, respectively.
参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《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：按人类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
No specific investigation on the absolute bioavailability of medroxyprogesterone (MPA) in humans has been conducted. MPA is rapidly absorbed from the gastrointestinal tract, and maximum MPA concentrations are obtained between 2 to 4 hours after oral administration.
Administration of medroxyprogesterone acetate with food increases the bioavailability of MPA. A 10 mg dose of medroxyprogesterone acetate, taken immediately before or after a meal, increased MPA Cmax (50 to 70%) and AUC (18 to 33%). The half-life of MPA was not changed with food.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
甲羟孕酮大约90%与蛋白质结合，主要与白蛋白结合；没有甲羟孕酮与性激素结合球蛋白的结合发生。
Medroxyprogesterone is approximately 90% protein bound, primarily to albumin; no MPA binding occurs with sex hormone binding globulin.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
大多数 MPA 代谢物以葡萄糖醛酸苷的形式通过尿液排出，只有少量以硫酸盐形式排出。
Most MPA metabolites are excreted in the urine as glucuronide conjugates with only minor amounts excreted as sulfates.
[EN] S-NITROSOMERCAPTO COMPOUNDS AND RELATED DERIVATIVES<br/>[FR] COMPOSÉS DE S-NITROSOMERCAPTO ET DÉRIVÉS APPARENTÉS
申请人：GALLEON PHARMACEUTICALS INC
公开号：WO2009151744A1
公开（公告）日：2009-12-17
The present invention is directed to mercapto-based and S- nitrosomercapto-based SNO compounds and their derivatives, and their use in treating a lack of normal breathing control, including the treatment of apnea and hypoventilation associated with sleep, obesity, certain medicines and other medical conditions.
[EN] COMPOUNDS AND METHODS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
申请人：TAVARES FRANCIS XAVIER
公开号：WO2016168118A1
公开（公告）日：2016-10-20
Novel compounds of formula (II) are disclosed. Compounds of formula (II) comprise ornithine derivatives or compounds that may metabolize to ornithine. Also disclosed are methods for the treatment of neurodegenerative diseases such as Alzheimer's Disease using compounds of formula (II).
[EN] COMPOUNDS AS MODULATORS OF TIGIT SIGNALLING PATHWAY<br/>[FR] COMPOSÉS MODULATEURS DE LA VOIE DE SIGNALISATION DE TIGIT
申请人：AURIGENE DISCOVERY TECH LTD
公开号：WO2018047139A1
公开（公告）日：2018-03-15
The present invention relates to compound of formula (I) as therapeutic agents to modulate the TIGIT signalling pathway. The invention also encompasses the use of the compound of formula (I) or a stereoisomer thereof or a pharmaceutically acceptable salt thereof for the treatment of diseases or disorders mediated by TIGIT.
[EN] NEW 6-AMINO-QUINOLINONE COMPOUNDS AND DERIVATIVES AS BCL6 INHIBITORS<br/>[FR] NOUVEAUX COMPOSÉS 6-AMINO-QUINOLINONE ET DÉRIVÉS EN TANT QU'INHIBITEURS DE BCL6
申请人：BOEHRINGER INGELHEIM INT
公开号：WO2018108704A1
公开（公告）日：2018-06-21
The present invention encompasses compounds of formula (I), wherein the groups R1 to R5, X, Y and W have the meanings given in the claims and specification, their use as inhibitors of BCL6, pharmaceutical compositions which contain compounds of this kind and their use as medicaments, especially as agents for treatment and/or prevention of oncological diseases.
[EN] COMBINATIONS OF INHIBITORS OF IRAK4 WITH INHIBITORS OF BTK<br/>[FR] COMBINAISONS D'INHIBITEURS DE L'IRAK4 À L'AIDE D'INHIBITEURS DE LA BTK
申请人：BAYER PHARMA AG
公开号：WO2016174183A1
公开（公告）日：2016-11-03
The present application relates to novel combinations of at least two components, component A and component B: · component A is an IRAK4-inhibiting compound of the formula (I) as defined herein, or a diastereomer, an enantiomer, a metabolite, a salt, a solvate or a solvate of a salt thereof; · component B is a BTK-inhibiting compound, or a pharmaceutically acceptable salt thereof; and, optionally, · one or more components C which are pharmaceutical products; in which one or two of the above-defined compounds A and B are optionally present in pharmaceutical formulations ready for simultaneous, separate or sequential administration, for treatment and/or prophylaxis of diseases, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially for treatment and/or prophylaxis of endometriosis, lymphoma, macular degeneration, COPD, neoplastic disorders and psoriasis.
