Approximately 10-30% of an oral dose of methenamine is hydrolyzed by gastric acidity to formaldehyde and ammonia. When methenamine mandelate is administered as enteric-coated tablets, the percentage of the dose hydrolyzed in the GI tract and the rate of absorption of the drug are reduced.
Within 24 hours, 70-90% or more of a single oral dose of methenamine or one of its salts is excreted intact in the urine by glomerular filtration and tubular secretion. When the urine is acidic, methenamine is hydrolyzed to formaldehyde and ammonia; maximum hydrolysis occurs when urine pH is 5.5 or less.
Methenamine hippurate was administered orally as tablets or granules to healthy volunteers. Plasma concentrations of methenamine reached a maximum 1--2 hours after a single dose and then declined with a half-life of about 4 hours. The apparent distribution volume was similar to that of total body water. Renal clearance of methenamine was somewhat lower than that of creatinine. In cross-over experiments over six days, methenamine recovered in the urine corresponded to about 80 per cent of the dose given per 12 hours, slightly lower values being obtained from granules than from tablets. The efficient renal elimination of methenamine was confirmed in similar studies on patients post-operatively. Methenamine hippurate was also given to healthy pregnant women during labor, a few hours before expected delivery. Methenamine was found to pass the placental barrier. The concentration of methenamine in umbilical cord plasma was low but reached the level in maternal plasma after about 4 hours. In amniotic fluid the methenamine concentration was low and varying. No correlation was obtained to the maternal or umbilical cord plasma levels.
来源:Hazardous Substances Data Bank (HSDB)
代谢
甲硝唑及其盐类在尿液中迅速排泄，如果尿液呈酸性，甲硝唑在尿液中会转化为甲醛和氨。
Methenamine & its salts are...rapidly excreted in urine where, providing the urine is acidic, methenamine is transformed to formaldehyde & ammonia.
IDENTIFICATION AND USE: Methenamine is a white or colorless crystalline solid. It is an anti-infective agent. Methenamine hippurate tablets, USP are indicated for prophylactic or suppressive treatment of frequently recurring urinary tract infections when long-term therapy is considered necessary. Non-medical uses include the following: in adhesives, coatings, and sealing compounds; as cross-linking agent for hardening phenol-formaldehyde resin and vulcanizing rubber; as corrosion inhibitor for steel; as fuel tablets for camping stoves; as stabilizer for lubricating and insulating oils; in the chemical detection of metals; in the preservation of hides; as dye fixative; for the manufacture of explosive compounds; antimicrobial food additive. HUMAN EXPOSURE AND TOXICITY: GI distress frequently is caused by doses >500 mg four times a day, even with enteric coated tablets. Painful and frequent micturition, albuminuria, hematuria, and rashes may result from doses of 4 to 8 g/day given for longer than 3-4 weeks. Inhalation may cause asthma-like reactions in previously sensitized individuals. Vapors or solutions have produced skin irritation. Methenamine does not appear to be linked to congenital defects. ANIMAL STUDIES: Studies on rats, mice, cats, and guinea pigs suggest that methenamine is moderately toxic following acute exposure. Mild irritation occurred when a 5% solution of a mixture that contained 40% methenamine was placed on the skin of guinea pigs. In chronic toxicity studies in dogs and rats receiving oral methenamine, gastric and bladder irritation occurred with some hemorrhagic sites and ulceration. Methenamine hippurate has been administered to rats for 12 months and to monkeys for 6 months at dosages equivalent to twice the usual recommended human dosage without evidence of adverse effects. Dogs have received single IV dosages of up to 600 mg/kg of methenamine hippurate without overt toxic effects.
In prospective controlled trials, methenamine was generally well tolerated at conventional doses and no episodes of serum aminotransferase elevations or clinically apparent liver injury were reported. Since its approval and in over 100 years of general use, there have been no reports of clinically apparent liver injury attributable to methenamine. Thus, clinically apparent liver injury from methenamine must be rare if it occurs at all.
来源:LiverTox
毒理性
致癌物分类
对人类无致癌性（未列入国际癌症研究机构IARC清单）。
No indication of carcinogenicity to humans (not listed by IARC).
◉ Summary of Use during Lactation:Both the hippurate and mandelate salts of methenamine pass into milk in small quantities and appear acceptable to use, even while nursing a newborn.
◉ Effects in Breastfed Infants:Four newborn infants were allowed to breastfeed in one study after a maternal dose of 1 gram of methenamine hippurate. No adverse effects were reported.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
来源:Drugs and Lactation Database (LactMed)
毒理性
暴露途径
该物质可以通过吸入其气溶胶和通过摄入被身体吸收。
The substance can be absorbed into the body by inhalation of its aerosol and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
吸收、分配和排泄
吸收
口服给药后，乌洛托品会被迅速吸收。（1）
After oral administration, rapid absorption of methenamine occurs. (1)
来源:DrugBank
吸收、分配和排泄
消除途径
Methenamine主要通过肾脏消除。(1)
Methenamine is primarily eliminated via the kidneys. (1)
来源:DrugBank
吸收、分配和排泄
清除
70-90%的单次口服剂量甲基胺在24小时内以原形从尿液中排出。(1)
70-90% of a single oral dose of methenamine is excreted unchanged in the urine within 24 hours. (1)
N-denitration of nitramines by dihydronicotinamides
摘要：
N-NO2 bond scission in organic nitramines occurs in high yields by reaction with 1,4-dihydronicotinamides. HMX (3) and tetryl (4) were used as model aliphatic and aromatic nitramines in reactions with 1-benzyl-1,4-dihydronicotinamide (BNAH, 1), resulting in hexamethylenetetramine and N-methylpicramide (5), respectively, as the predominant products. Radical initiation of the electron-transfer deniaohydrogenation mechanism is achieved either by photolysis or chemically by dithionite ion. A polymer-supported analogue of BNAH effects similar, though slower, N-denitration. Copyright (C) 1996 Elsevier Science Ltd.
[EN] DIHYDROPYRROLONAPHTYRIDINONE COMPOUNDS AS INHIBITORS OF JAK<br/>[FR] COMPOSÉS DE DIHYDROPYRROLONAPHTYRIDINONE COMME INHIBITEURS DE JAK
申请人：TAKEDA PHARMACEUTICAL
公开号：WO2010144486A1
公开（公告）日：2010-12-16
Disclosed are JAK inhibitors of formula (I) where G1, R1, R2, R3, R4, R5, R6, and R7 are defined in the specification. Also disclosed are pharmaceutical compositions, kits and articles of manufacture which contain the compounds, methods and materials for making the compounds, and methods of using the compounds to treat diseases, disorders, and conditions involving the immune system and inflammation, including rheumatoid arthritis, hematological malignancies, epithelial cancers (i.e., carcinomas), and other diseases, disorders or conditions associated with JAK.
[EN] PREPARATION AND USES OF REACTIVE OXYGEN SPECIES SCAVENGER DERIVATIVES<br/>[FR] PRÉPARATION ET UTILISATIONS DE DÉRIVÉS PIÉGEURS D'ESPÈCES RÉACTIVES DE L'OXYGÈNE
申请人：XW LAB INC
公开号：WO2019033330A1
公开（公告）日：2019-02-21
Compounds of Formula (I) a or (I) b: including certain quinone derivatives, and the corresponding pharmaceutical compositions, which may serve to modulate ferroptosis in a subject. Also disclosed herein are the preparations of these compounds and pharmaceutical compositions and their potential uses in the manufacture of a medicament in reducing reactive oxygen species (ROS) in a cell and for preventing, treating, ameliorating certain related disorder or a disease.
New Drug Delivery System for Crossing the Blood Brain Barrier
申请人：Lipshutz H. Bruce
公开号：US20070203080A1
公开（公告）日：2007-08-30
New ubiquinol analogs are disclosed, as well as methods of using these compounds to deliver drug moieties to the body.
新的泛醌类似物被披露，以及利用这些化合物将药物基团输送到人体的方法。
METHOD FOR PRODUCING AMINONITRILES
申请人：Oftring Alfred
公开号：US20100016625A1
公开（公告）日：2010-01-21
The invention relates to a process for preparing an amino nitrile mixture comprising aminoacetonitrile (AAN) and from 5 to 70% by weight of iminodiacetonitrile (IDAN), which comprises heating crude AAN which is largely free of formaldehyde cyanohydrin (FACH-free) at a temperature of from 50 to 150° C.
