Metabolized in the liver principally via oxidation of the p-methyl group producing the carboxyl metabolite, 1-butyl-3-p-carboxyphenylsulfonylurea. May also be metabolized to hydroxytolbutamide. Tolbutamide does not undergo acetylation like antibacterial sulfonamides as it does not have a p-amino group.
...MAJOR TOLBUTAMIDE METAB IN MAN HAS BEEN IDENTIFIED AS 1-BUTYL-3-P-CARBOXYPHENYLSULFONYLUREA... 1-BUTYL-3-P-HYDROXYMETHYLPHENYLSULFONYLUREA IS ALSO FORMED IN SMALL AMT.
IN RAT, MAJOR URINARY METAB, 1-BUTYL-3-P-HYDROXYMETHYLPHENYLSULFONYLUREA COMPRISED 75% OF DOSE, BUT SMALL AMT OF 1-BUTYL-3-P-CARBOXYPHENYLSULFONYLUREA & P-TOLYLSULFONYLUREA, COMPRISING 5% OF DOSE, WERE ALSO PRESENT.
ALTHOUGH 1-BUTYL-3-P-HYDROXYMETHYLPHENYLSULFONYLUREA HAS BEEN REPORTED AS PRINCIPAL METAB IN CAT.../IT IS CLAIMED/ THAT CAT METABOLIZES TOLBUTAMIDE IN SAME WAY AS DOG. .../IT HAS BEEN SHOWN/ THAT TOLBUTAMIDE IS TRANSFORMED INTO 1-BUTYL-3-P-CARBOXYPHENYLSULFONYLUREA IN GUINEA PIGS & RABBITS.
来源:Hazardous Substances Data Bank (HSDB)
代谢
与大鼠、兔子和人类相比，狗通过涉及水解的机制将妥布他米代谢成对甲苯磺酰脲和对甲苯磺酰胺。
IN CONTRAST TO RATS, RABBITS & MAN, DOGS METABOLIZE TOLBUTAMIDE...INTO P-TOLYLSULFONYLUREA & P-TOLYLSULFONAMIDE BY MECHANISM INVOLVING HYDROLYSIS.
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
Readily absorbed following oral administration. Tolbutamide is detectable in plasma 30-60 minutes following oral administration of a single dose with peak plasma concentrations occurring within 3-5 hours. Absorption is unaltered if taken with food but is increased with high pH.
Unchanged drug and metabolites are eliminated in the urine and feces. Approximately 75-85% of a single orally administered dose is excreted in the urine principally as the 1-butyl-3-p-carboxyphenylsulfonylurea within 24 hours.
来源:DrugBank
吸收、分配和排泄
口服给药后，磺酰脲类药物迅速吸收。/磺酰脲类药物/
AFTER ORAL ADMIN, SULFONYLUREAS ARE RAPIDLY ABSORBED. /SULFONYLUREAS/
TOLBUTAMIDE CAN BE DETECTED IN BLOOD WITHIN 30 MIN AFTER ORAL ADMIN; PEAK CONCN ARE REACHED WITHIN 3 TO 5 HR. .../IT/ IS BOUND TO PLASMA PROTEINS. ... HALF-LIFE OF TOLBUTAMIDE IS ABOUT 5 HR.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
与动物研究中报告的情况相比，人体对甲苯磺丁脲的代谢清除率在禁食状态下并未改变。
IN CONTRAST TO STUDIES REPORTED IN ANIMALS, METABOLIC CLEARANCE OF...TOLBUTAMIDE IN MAN HAS BEEN SHOWN TO BE UNALTERED BY FASTING.
[EN] BENZAMIDE OR BENZAMINE COMPOUNDS USEFUL AS ANTICANCER AGENTS FOR THE TREATMENT OF HUMAN CANCERS<br/>[FR] COMPOSÉS BENZAMIDE OU BENZAMINE À UTILISER EN TANT QU'ANTICANCÉREUX POUR LE TRAITEMENT DE CANCERS HUMAINS
申请人：UNIV TEXAS
公开号：WO2017007634A1
公开（公告）日：2017-01-12
The described invention provides small molecule anti-cancer compounds for treating tumors that respond to cholesterol biosynthesis inhibition. The compounds selectively inhibit the cholesterol biosynthetic pathway in tumor-derived cancer cells, but do not affect normally dividing cells.
[EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
申请人：GILEAD APOLLO LLC
公开号：WO2017075056A1
公开（公告）日：2017-05-04
The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
[EN] SULFONYL COMPOUNDS THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN<br/>[FR] COMPOSÉS DE SULFONYLE QUI INTERAGISSENT AVEC LA PROTÉINE RÉGULATRICE DE LA GLUCOKINASE
申请人：AMGEN INC
公开号：WO2013123444A1
公开（公告）日：2013-08-22
The present invention relates to sulfonyl compounds that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.
SULFOXIMINE SUBSTITUTED QUINAZOLINES FOR PHARMACEUTICAL COMPOSITIONS
申请人：BLUM Andreas
公开号：US20140135309A1
公开（公告）日：2014-05-15
This invention relates to novel sulfoximine substituted quinazoline derivatives of formula I
wherein Ar, R
1
and R
2
are as defined herein, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.
[EN] SULFOXIMINE SUBSTITUTED QUINAZOLINES FOR PHARMACEUTICAL COMPOSITIONS<br/>[FR] QUINAZOLINES SUBSTITUÉES PAR SULFOXIMINE POUR COMPOSITIONS PHARMACEUTIQUES
申请人：BOEHRINGER INGELHEIM INT
公开号：WO2014072244A1
公开（公告）日：2014-05-15
This invention relates to novel sulfoximine substituted quinazoline derivatives of formula (I), wherein Ar, R1 and R2 are as defined in the description and claims, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.
