Tioconazole

Tioconazole is an imidazole derivative. It’s chemical name is (RS)1[2-[(2-Chloro-3-thienyl)methoxy]2(2,4-dichlorophenyl)ethyl]-1H-imidazole and its molecular weight is 387.7. Tioconazole is a white or almost white, crystalline powder which is slightly soluble in water but very soluble in methanol, ethanol and chloroform.

Tioconazole is a broad spectrum antifungal agent that also has an antibacterial effect on a number of Gram-positive cocci (e.g. Stapphylococcus, Streptococcus species). It is active against commonly occurring dermatophyte and yeast-like fungal species. It is fungicidal in murine models vs. Candida spp., T. rubrum and T. mentacrophytes. In vitro it is fungicidal to pathenogenic dermatophytes, yeasts and other fungi. All dermatophytes and Candida spp. were inhibited by 6.25 or 12.5 mg/l respectively. It is also inhibitory vs. Staph. spp. and Strep. spp. at 100 mg/l or less.

Absorption

Absorption is rapid and extensive on oral administration to rats, monkeys and man, the major metabolite being a glucuronide conjugate of tioconazole. Tissue uptake in rat and monkey was highest in liver, kidney and intestinal tract with excretion in all species mainly in faeces.

Rat studies using oral, dermal and vaginal administration of C¹⁴ labelled tioconazole confirm significantly lower absorption via the topical route.

In man, oral formulations of tioconazole (500mg) gave plasma concentrations of 1300ng/ml. Topical administration of dermal cream 1% (20mg/day) for 28 days, or vaginal cream 2% (100mg/day) for 30 days gave negligible mean peak plasma levels, i.e. 10.1 and 11.5ng/ml respectively.

After single dose administration of tioconazole vaginal ointment 6.5% w/w (tioconazole 300mg) the mean peak plasma concentration was 18ng/ml in humans, achieved approximately 8 hours post dose.

Tioconazole cream applied on rat and rabbit skin did not result in systemic toxicity in these animals. Mild topical reaction was observed.

Oral doses (200 mg/kg) did not affect behaviour in rats but 25 mg/kg i.v. produced dose-related respiratory distress, gasping, tremors and prostration. Slight but dose- related impairment of performance of mice on the rotating rod occurred from 25 mg/kg. Slight anti-cholinergic and anti-histamine (H1) activity was recorded in vitro but no effect on mice pupil size in vivo. Oral tioconazole prolonged alcohol and pentobarbital sleeping time at 150 and 37.5 mg/kg respectively.

In the anaesthetised cat i.v. tioconazole 2.5-10 mg/kg produced brief falls in blood pressure and increased heart rate, haematuria, tremors and twitches.