チニダゾール

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Antibiotics

log Kow = -0.35

0.7

-0.38

3.03e+00 g/L

>37.1 [ug/mL] (The mean of the results at pH 7.4)

Breast Feeding; Lactation; Anti-Infective Agents; Antibacterial Agents; Antiprotozoal Agents; Nitroimidazoles

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Antiamoebic and antigiardiasis medicines

127-128 °C

127-128 °C

127 - 128 °C

Warning

H312 (56.8%): Harmful in contact with skin [Warning Acute toxicity, dermal]

P203, P261, P271, P280, P302+P352, P304+P340, P317, P318, P321, P362+P364, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 74 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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.

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.

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.

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.

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).

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).

Drug Induced Liver Injury Rank (DILIrank 2.0)

Tinidazole

vLess-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

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 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).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Metronidazole, a chemically-related nitroimidazole, has been reported to be carcinogenic in mice and rats but not hamsters. In several studies metronidazole showed evidence of pulmonary, hepatic and lymphatic tumorigenesis in mice and mammary and hepatic tumors in female rats. Tinidazole carcinogenicity studies in rats, mice or hamsters have not been reported.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Embryo-fetal developmental toxicity studies in pregnant mice indicated no embryo-fetal toxicity or malformations at the highest dose level of 2,500 mg/kg.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Sixty-day fertility study done in male rats given doses (600 mg/kg/day) of tinidazole, resulting in reduced fertility and produced testicular histopathology. Spermatogenic effects resulted from dose levels of 300 and 600 mg/kg/day, while the no observed adverse effects dose level was 100 mg/kg/day. These effects are characteristic of agents in the 5-nitroimidazole class.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In a study with pregnant rats a slightly higher incidence of fetal mortality was observed at a maternal dose of 500 mg/kg. No biologically relevant neonatal developmental effects were observed in rat neonates following maternal doses as high as 600 mg/kg.

/GENOTOXICITY/ Tinidazole was found to be mutagenic in the TA100, S. typhimurium testere strain both with and without the metabolic activation system and was not mutagenic in the TA98 strain. However mutagenicity results were mixed both positive and negative in the TA1535, 1537, and 1538 strains. Tinidazole was also positive in a tester strain of Klebsiella pneumonia and positive for in vivo genotoxicity in the mouse micronucleus assay. Tinidazole was negative for mutagenicity in a mammalian cell culture system with Chinese hamster lung V79 cells and negative for genotoxicity in the Chinese hamster ovary sister chromatid exchange assay.

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).

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)

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.

J01XD02

P - Antiparasitic products, insecticides and repellents

J - Antiinfectives for systemic use

G - Genito urinary system and sex hormones

QG - Genito urinary system and sex hormones

QJ - Antiinfectives for systemic use

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

Tinidazole is a prodrug and antiprotozoal agent. The nitro group of tinidazole is reduced in <i>Trichomonas</i> 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 <i>Giardia</i> and <i>Entamoeba</i> 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.

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.

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.

033KF7V46H

TINIDAZOLE

Established Pharmacologic Class [EPC] - Nitroimidazole Antimicrobial

Chemical Structure [CS] - Nitroimidazoles

Tinidazole is a Nitroimidazole Antimicrobial.

TINIDAZOLE

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.

Agents used to treat trichomonas infections.

Substances that inhibit the growth or reproduction of BACTERIA.

Rapidly and completely absorbed under fasting conditions. Administration with food results in a delay in Tmax of approximately 2 hours and a decline in Cmax 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)

MEDICATION

Antitrichomonal Agents

Antiprotozoal and antibacterial activity