KETODERM Cream Ref.[27880] Active ingredients: Ketoconazole

The systemic absorption of Ketoconazole cream 2% was not measurable in Beagle dogs. When applied to both intact and abraded skin at a daily dose of 80 mg for 28 days, the cream produced plasma levels of ketoconazole which did not exceed the detection limit of the HPLC-method (0.002μg/mL).

The systemic absorption of Ketoconazole cream 2% was not detectable in man. A single application of 10 g cream to the back, arms and chest did not produce quantifiable blood levels.

Animal Studies

Subacute Dermal Toxicity in New Zealand White Rabbits and Albino Guinea Pigs

Ketoconazole cream 2% at doses of 0, 0.5, 1.0 and 2.0 g/kg was devoid of any irritating effect in 16 male and 16 female New Zealand white rabbits (4 per group). Daily applications to the intact or abraded skin up to 2 g/kg for 30 days produced a barely perceptible irritation that was no different from that with 2 g/kg of the vehicle; a single application of 0.1 mg to the conjunctiva of 6 male New Zealand white rabbits was not irritating.

Ketoconazole cream 2% was also devoid of any allergenic or sensitizing potential in 10 male and 10 female albino guinea pigs. Induction comprised 10 topical applications of 0.5 mg Ketoconazole cream 2% using occlusive patches and 2 intradermal injections of Freund’s complete adjuvant over a 4 week period. Subsequently, animals were challenged with a single 48-hour application of the same dose. This dose was applied to a region which had not been previously treated. Neither the patches used for the induction experiment nor those used in the challenge reaction elicited oedema or erythema.

Carcinogenicity

When ketoconazole was admixed in the diet, such that daily oral doses up to 80 mg/kg/day were provided to Swiss Albino mice for a period of 18 months and also to Wistar rats for a period of 24 months, there was no evidence of oncogenic activity.

Mutagenicity

The dominant lethal mutation test in male and female mice revealed that single oral doses of ketoconazole as high as 80 mg/kg produced no mutation at any stage of germ cell development. The Ames Salmonella microsomal activator assay was also negative.

Reproduction and Teratology

Ketoconazole has been shown to be embryotoxic and teratogenic (syndactylia and oligodactylia) in the rat when given in the diet at 80 mg/kg/day. When ketoconazole was given to rats by gavage, evidence of maternal toxicity and embryotoxicity was seen with doses as low as 10 mg/kg.

Human Studies

Dermal Irritancy

In 10 female volunteers treated topically with 5μg/cm² Ketoconazole cream 2%, exposure to longwave ultraviolet or visible light did not produce any wheel and flare reaction.

Twenty-five volunteers received a series of 6 applications (2 per week) of 10μg/cm² of Ketoconazole cream 2% on an occlusive dressing applied to the back skin for 24 hours. Following removal of the patch, the skin was exposed to three minimal erythema doses from a Xenon Solar Simulator. Ten days after the last exposure the subjects were challenged with 5μg/cm² Ketoconazole cream 2% applied to an untreated site of the skin for 24 hours and subsequently exposed to long ultraviolet light. Ketoconazole cream 2% was shown to be devoid of any detectable photocontact allergenic potential.