1H-Imidazole, 1-[2-(ethylsulfonyl)ethyl]-2-methyl-5-nitro-, radical ion(1-)

247.27 g/mol

247.06267708 g/mol

243-014-4

033KF7V46H

758189

DTXSID4023676

C890

Colorless crystals from benzene

J01XD02|J - Antiinfectives for systemic use|P - Antiparasitic products, insecticides and repellents

106 Ų

-0.35 (LogP)|log Kow = -0.35|0.7

127-128 °C|127.5 °C|127-128°C

>37.1 [ug/mL]|In water, 2.0X10+4 mg/L at 25 °C (est)|3.03e+00 g/L

2.7X10-7 mm Hg at 25 °C (est)

Henry's Law constant = 5.2X10-11 atm-cu m/mol at 25 °C (est)

pKa = 4.7 (sp2 hybridized imidazole nitrogen) (est)

149.7 Ų [M+H]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]|161.2 Ų [M+Na]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]

Hydroxyl radical reaction rate constant = 2.2X10-11 cu cm/molecule-sec at 25 °C (est)

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl tinidazole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Manes G, Balzano A.; Tinidazole: From Protozoa to Helicobacter Pylori--The Past, Present and Future of a Nitroimidazole with Peculiarities; Expert Rev Anti Infect Ther 2 (5): 695-705 (2004)

|Warning|H312 (56.94%): Harmful in contact with skin [Warning Acute toxicity, dermal]|P201, P202, P261, P271, P280, P281, P302+P352, P304+P312, P304+P340, P308+P313, P312, P322, P363, P405, and P501|Aggregated GHS information provided by 72 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

There are no reported overdoses with tinidazole in humans. In acute studies with mice and rats, the LD 50 for mice was generally > 3,600 mg/kg for oral administration and was > 2,300 mg/kg for intraperitoneal administration. In rats, the LD 50 was > 2,000 mg/kg for both oral and intraperitoneal administration.

Tinidazole is typically given for a few days only, but serum enzyme elevations have been reported with its use, and serum enzyme elevations during therapy is listed as a possible adverse event in the product label. Tinidazole is also capable of causing anaphylactic and allergic reactions including urticaria, angioedema and bronchospasm, reactions which can be associated with minor serum enzyme elevations. Tinidazole, despite considerable use worldwide, has not been linked convincingly to instances of clinically apparent liver injury with jaundice.

Cholestyramine may decrease oral bioavailability; separate dosing of cholestyramine and tinidazole is recommended.|Effects may be enhanced when these agents /coumarin anticoagulants/ are used concurrently with tinidazole resulting in prolongation of prothrombin time; dosage of oral anticoagulants may need to be adjusted during tinidazole therapy and up to 8 days after discontinuation.|It is recommended that these substances /ethyl alcohol, ethanol-containing preparations, propylene glycol/ not be used concurrently with tinidazole, or for 3 days following tinidazole therapy; abdominal cramps, nausea, vomiting, headache, or flushing may occur.|Concomitant administration /of intravenous phenytoin or intravenous fosphenytoin/ with tinidazole increases half life and decreases clearance of phenytoin.|For more Interactions (Complete) data for TINIDAZOLE (11 total), please visit the HSDB record page.

LD50 Mouse acute > 3,600 mg/kg|LD50 Mouse ip > 2,300 mg/kg|LD50 Rat oral > 2,000 mg/kg|LD50 Rat ip > 2,000 mg/kg

Plasma protein binding of tinidazole is 12%.

Tinidazole's production and use as an antiprotozoal agent(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 15(SRC), determined from a log Kow of -0.35(2) and a regression-derived equation(3), indicates that tinidazole is expected to have very high mobility in soil(SRC). The estimated pKa of tinidazole is 4.7 (sp2 hybridized imidazole nitrogen)(4), indicating that this compound will exist partially as a cation in the environment under acidic conditions and cations generally have lower mobility in soil than their neutral counterparts(5). Volatilization of tinidazole from moist soil surfaces is not expected to be an important fate process(SRC) because cations do not volatilize and based on an estimated Henry's Law constant of 5.2X10-11 atm-cu m/mole(SRC), calculated using a fragment constant estimation method(6). Tinidazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.7X10-7 mm Hg(SRC), determined from a fragment constant method(7). Biodegradation data were not available(SRC, 2005).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 15(SRC), determined from a log Kow of -0.35(2) and a regression-derived equation(3), indicates that tinidazole is not expected to adsorb to suspended solids and sediment(SRC). The estimated pKa of tinidazole is 4.7 (sp2 hybridized imidazole nitrogen)(3), indicating that this compound will exist partially as a cation in the environment under acidic conditions and cations generally adsorb more strongly to sediment than their neutral counterparts(4). Volatilization from water surfaces is not expected(5) because cations do not volatilize and based upon an estimated Henry's Law constant of 5.2X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(6). According to a classification scheme(7), an estimated BCF of <1(SRC), from the measured log Kow(2) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2005).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), tinidazole, which has an estimated vapor pressure of 2.7X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase tinidazole may be removed from the air by wet or dry deposition(SRC). Tinidazole does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Tinidazole is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Tinidazole does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of <1 was calculated for tinidazole(SRC), using a log Kow of -0.35(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of tinidazole is estimated as 15(SRC), using a log Kow of -0.35(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that tinidazole is expected to have very high mobility in soil. The estimated pKa of tinidazole is 4.7 (sp2 hybridized imidazole nitrogen)(4), indicating that this compound will partially exist in the cation form in the environment under acidic conditions and cations generally have lower mobility in soil than their neutral counterparts(5).

The Henry's Law constant for tinidazole is estimated as 5.2X10-11 atm-cu m/mole(SRC) using a fragment constant estimation method(1). The estimated pKa of tinidazole is 4.7 (sp2 hybridized imidazole nitrogen)(2), indicating that this compound will exist partially as a cation in the environment under acidic conditions. Based on this Henry's Law constant and the fact that cations do not volatilize, tinidazole is expected to be essentially nonvolatile from moist soil and water surfaces(3). Tinidazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.7X10-7 mm Hg(SRC), determined from a fragment constant method(4).

While data specific to tinidazole were not located(SRC, 2006), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

Tinidazole is distributed into breast milk at concentrations similar to those in serum.

Occupational exposure to tinidazole may occur through inhalation and dermal contact with this compound at workplaces where tinidazole is produced or used. Exposure to tinidazole among the general population may be limited to those administered this substance as a drug. (SRC)

For the treatment of trichomoniasis caused by T. vaginalis in both female and male patients. Also for the treatment of giardiasis caused by G. duodenalis in both adults and pediatric patients older than three years of age and for the treatment of intestinal amebiasis and amebic liver abscess caused by E. histolytica in both adults and pediatric patients older than three years of age.|FDA Label

Tinidazole is an orally available, broad spectrum antimicrobial agent used in the treatment of bacterial, protozoal and parasitic infections. Tinidazole is a nitroimidazole similar to metronidazole and is likely to have a similar spectrum and frequency of side effects, including a low rate of serum enzyme elevations during therapy and rare instances of clinically apparent acute liver injury.

Antiinfective Agents

Antitrichomonal Agents|MEDICATION: Antiprotozoal (Trichomonas, Giardia); antiamebic; antibacterial|Oral tinidazole is indicated in the treatment of amebic liver abscess caused by Entamoeba histolytica in both adults and pediatric patients older than three years of age. /Included in US product labeling/|Oral tinidazole is indicated in the treatment of intestinal amebiasis caused by Entamoeba histolytica in both adults and pediatric patients older than three years of age. /Included in US product labeling/|For more Therapeutic Uses (Complete) data for TINIDAZOLE (6 total), please visit the HSDB record page.

Tinidazole is distributed into breast milk at concentrations similar to those in serum. Because tinidazole can be detected in breast milk for up to 72 hours after administration, interruption of breast-feeding during tinidazole therapy and for three days following the last dose is recommended.|FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./|Tinidazole crosses the placenta, and enters the fetal circulation. Therefore, it should not be administered to pregnant women during the first trimester.|Adverse effects occurring in 1% or more of patients receiving tinidazole include GI effects (metallic/bitter taste, nausea, anorexia, dyspepsia/cramps/epigastric discomfort, vomiting, constipation) and nervous system effects (weakness/fatigue/malaise, dizziness, headache).|For more Drug Warnings (Complete) data for TINIDAZOLE (11 total), please visit the HSDB record page.

Tinidazole is a synthetic antiprotozoal agent. Tinidazole demonstrates activity both in vitro and in clinical infections against the following protozoa: Trichomonas vaginalis, Giardia duodenalis (also termed G. lamblia), and Entamoeba histolytica. Tinidazole does not appear to have activity against most strains of vaginal lactobacilli.

Agents used to treat trichomonas infections. (See all compounds classified as Antitrichomonal Agents.)|Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)|Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. (See all compounds classified as Alkylating Agents.)

Rapidly and completely absorbed under fasting conditions. Administration with food results in a delay in T_max of approximately 2 hours and a decline in C_max of approximately 10% and an AUC of 901.6 ± 126.5 mcg hr/mL.|Tinidazole crosses the placental barrier and is secreted in breast milk. Tinidazole is excreted by the liver and the kidneys. Tinidazole is excreted in the urine mainly as unchanged drug (approximately 20-25% of the administered dose). Approximately 12% of the drug is excreted in the feces.|50 L|Tinidazole is distributed into virtually all tissues and body fluids. Tinidazole also crosses the blood-brain barrier, placental barrier and is distributed into breast milk. Volume of distribution (VolD): about 50 L.|Under fasted conditions tinidazole is rapidly and completely absorbed. Administration with food resulted in a delay in Tmax of approximately 2 hours and a decline in Cmax of approximately 10% and an AUC of 901.6 + or - 126.5 ug hr/mL.|Time to peak concentration: 1.6 (+ or - 0.7 hours)|Elimination: Renal: 20 to 25% as unchanged drug. Fecal: 12%. In hemodialysis: 43% eliminated during 6 hour hemodialysis session.|For more Absorption, Distribution and Excretion (Complete) data for TINIDAZOLE (6 total), please visit the HSDB record page.

Hepatic, mainly via CYP3A4. Tinidazole, like metronidazole, is significantly metabolized in humans prior to excretion. Tinidazole is partly metabolized by oxidation, hydroxylation and conjugation. Tinidazole is the major drug-related constituent in plasma after human treatment, along with a small amount of the 2-hydroxymethyl metabolite.|Tinidazole, like metronidazole, is significantly metabolized in humans prior to excretion. Tinidazole is partly metabolized by oxidation, hydroxylation and conjugation. Tinidazole is the major drug-related constituent in plasma after human treatment, along with a small amount of the 2-hydroxymethyl metabolite. Tinidazole is biotransformed mainly by CYP3A4. In an in vitro metabolic drug interaction study, tinidazole concentrations of up to 75 ug/mL did not inhibit the enzyme activities of CYP1A2, CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4.

The elimination half-life is 13.2±1.4 hours and the plasma half-life is 12 to 14 hours.|Elimination: 13.2 (+ or - 1.4) hours. Plasma: approximately 12 to 14 hours.

Tinidazole is a prodrug and antiprotozoal agent. The nitro group of tinidazole is reduced in Trichomonas by a ferredoxin-mediated electron transport system. The free nitro radical generated as a result of this reduction is believed to be responsible for the antiprotozoal activity. It is suggested that the toxic free radicals covalently bind to DNA, causing DNA damage and leading to cell death. The mechanism by which tinidazole exhibits activity against Giardia and Entamoeba species is not known, though it is probably similar.|The nitro group of tinidazole is reduced by cell extracts of Trichomonas. As a result of this reduction a free nitro radical is generated which may be responsible for the antiprotozoal activity. The mechanism by which tinidazole exhibits activity against Giardia and Entamoeba species is not known.

There is no specific antidote for the treatment of overdosage with tinidazole; therefore, treatment should be symptomatic and supportive. Gastric lavage may be helpful. Hemodialysis can be considered because approximately 43% of the amount present in the body is eliminated during a 6-hour hemodialysis session.|/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

Bioshik

Oral: Tablets, film-coated: 250 mg Tindamax (scored), (Presutti); 500 mg Tindamax (scored), (Presutti).

Analyte: tinidazole; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: tinidazole; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards|Analyte: tinidazole; matrix: chemical identification; procedure: thin-layer chromatography with comparison to standards|Analyte: tinidazole; matrix: chemical purity; procedure: dissolution in glacial acetic acid; potentiometric titration with perchloric acid using a suitable electrode system

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals -> Animal Drugs -> Approved in Taiwan