Among the most potent antibacterial agents against the most drug-resistant anaerobic bacteria, Bacteroides fragilis, is tinidazole. Giardiasis, amebiasis, and trichomonal vaginitis are among the protozoal infections that tinidazole is effective against [1].

Absorption, Distribution and Excretion
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)
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.

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Metabolism / Metabolites
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.

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Biological Half-Life
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.

Hepatotoxicity
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.
Likelihood score: E* (suspected but unproven rare cause of clinically apparent liver injury)

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Amounts of tinidazole in milk are less than doses given to infants. Measurements of infant plasma levels during breastfeeding have not been reported. No studies have evaluated adverse effects of tinidazole on the infant during breastfeeding, but presumably they are similar to those of the closely related drug, metronidazole, such as increased risk of oral and rectal Candida infections.
As with metronidazole, concern has been raised about exposure of healthy infants to tinidazole via breastmilk, because of possible mutagenicity and carcinogenicity. Opinions vary among experts on the advisability of using tinidazole during longer-term therapy while breastfeeding, but avoidance of breastfeeding for 3 days after a single dose should allow milk levels to drop to negligible values. Other drugs are available for bacterial vaginosis, and can be given vaginally, which should result in lower amounts in breastmilk.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Plasma protein binding of tinidazole is 12%.

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Interactions
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.

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Non-Human Toxicity Values
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

[1]. Tinidazole--microbiology, pharmacology and efficacy in anaerobic infections. Infection. 1983;11(1):54-60.

Tinidazole is 1H-imidazole substituted at C-1 by a (2-ethylsulfonyl)ethyl group, at C-2 by a methyl group and at C-5 by a nitro group. It is used as an antiprotozoal, antibacterial agent. It has a role as an antiprotozoal drug, an antibacterial drug, an antiparasitic agent and an antiamoebic agent.
A nitroimidazole antitrichomonal agent effective against Trichomonas vaginalis, Entamoeba histolytica, and Giardia lamblia infections.
Tinidazole is a Nitroimidazole Antimicrobial.
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.
Tinidazole is a 5-nitroimidazole derivative with antiprotozoal property. Although the mechanism of action has not been fully elucidated, it has been suggested that tinidazole is metabolized and yields nitrite anions and metronidazole. Metronidazole's nitro group in turn is reduced via the parasite ferredoxin, thereby generating a series of free nitro radicals including nitro anions. Toxicity is achieved via depletion of sulfhydryl groups and DNA strand breaks with multiple hits having an additive effect and ultimately leading to cell death.
A nitroimidazole alkylating agent that is used as an antitrichomonal agent against TRICHOMONAS VAGINALIS; ENTAMOEBA HISTOLYTICA; and GIARDIA LAMBLIA infections. It also acts as an antibacterial agent for the treatment of BACTERIAL VAGINOSIS and anaerobic bacterial infections.

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Drug Indication
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

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Mechanism of Action
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.

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Therapeutic Uses
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.

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Drug Warnings
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.

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Pharmacodynamics
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.

C8H13N3O4S

247.2715

247.062

19387-91-8

Tinidazole-d5;1216767-04-2

5479

White to off-white solid powder

1.4±0.1 g/cm3

528.4±30.0 °C at 760 mmHg

117-121 °C(lit.)

273.4±24.6 °C

0.0±1.3 mmHg at 25°C

1.599

-0.27

0

5

4

16

345

0

S(C([H])([H])C([H])([H])[H])(C([H])([H])C([H])([H])N1C(=C([H])N=C1C([H])([H])[H])[N+](=O)[O-])(=O)=O

HJLSLZFTEKNLFI-UHFFFAOYSA-N

InChI=1S/C8H13N3O4S/c1-3-16(14,15)5-4-10-7(2)9-6-8(10)11(12)13/h6H,3-5H2,1-2H3

1-(2-ethylsulfonylethyl)-2-methyl-5-nitroimidazole

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 50 mg/mL (~202.21 mM)
H2O : ~3.33 mg/mL (~13.47 mM)

Solubility in Formulation 1: ≥ 3.25 mg/mL (13.14 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 3.25 mg/mL (13.14 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 3.25 mg/mL (13.14 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 2 mg/mL (8.09 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)