Tinidazole

The mode of action of tinidazole against anaerobic bacteria and protozoa involves penetration of the drug into the cell of the micro-organism and subsequent damage of DNA strands or inhibition of their synthesis.

Tinidazole is active against both protozoa and obligate anaerobic bacteria. The activity against protozoa involves Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia.

Tinidazole is active against Helicobacter pylori, Gardnerella vaginalis and most anaerobic bacteria including Bacteroides fragilis, Bacteroides melaninogenicus, Bacteroides spp., Clostridium spp., Eubacterium spp., Fusobacterium spp., Peptococcus spp., Peptostreptococcus spp. and Veillonella spp.

Helicobacter pylori (H.pylori) is associated with acid peptic disease including duodenal ulcer and gastric ulcer in which about 95% and 80% of patients respectively are infected with this agent. H.pylori is also implicated as a major contributing factor in the development of gastritis and ulcer recurrence in such patients. Evidence suggests a causative link between H.pylori and gastric carcinoma.

Clinical evidence has shown that the combination of tinidazole with omeprazole and clarithromycin eradicates 91-96% of H.pylori isolates.

Various different H.pylori eradication regimens have shown that eradication of H.pylori heals duodenal ulcers and reduces the risk of ulcer recurrence.

Tinidazole is rapidly and completely absorbed following oral administration. In studies with healthy volunteers receiving 2g tinidazole orally, peak serum levels of 40-51 micrograms/ml were achieved within two hours and decreased to between 11-19 micrograms/ml at 24 hours. Healthy volunteers who received 800mg and 1.6g tinidazole IV over 10-15 minutes achieved peak plasma concentrations that ranged from 14 to 21mcg/ml for the 800mg dose and averaged 32mcg/ml for the 1.6g dose. At 24 hours postinfusion, plasma levels of tinidazole decreased to 4-5mcg/ml and 8.6mcg/ml respectively, justifying once daily dosing. Plasma levels decline slowly and tinidazole can be detected in plasma at concentrations of up to 1 microgram/ml at 72 hours after oral administration. The plasma elimination half-life for tinidazole is between 12-14 hours.

Tinidazole is widely distributed in all body tissues and also crosses the blood brain barrier, obtaining clinically effective concentrations in all tissues. The apparent volume of distribution is about 50 litres. About 12% of plasma tinidazole is bound to plasma protein.

Tinidazole is excreted by the liver and kidneys. Studies in healthy patients have shown that over 5 days, 60-65% of an administered dose is excreted by the kidneys with 20-25% of the administered dose excreted as unchanged tinidazole. Up to 5% of the administered dose is excreted in the faeces.

Studies in patients with renal failure (creatinine clearance <22ml/min) indicate that there is no statistically significant change in tinidazole pharmacokinetic parameters in these patients.

Tinidazole has been shown to be mutagenic in some bacterial strains tested in vitro (with and without metabolic activation). Tinidazole was negative for mutagenicity in a mammalian cell culture system utilising Chinese hamster lung V79 cells (HGPRT test system) and negative for genotoxicity in the Chinese hamster ovary (CHO) sister chromatid exchange assay. Tinidazole was positive for in vivo genotoxicity in the mouse micronucleus assay.