Singapore Drugs Database

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.

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.

Pharmacokinetics

Absorption

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.

Distribution

* 50 L

Metabolism

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.

Elimination

Toxicity

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.

Active Ingredient/Synonyms

Timidazole | Tinidazole |