ATCvet code: QJ02AB02

Ketoconazole is an antifungal agent with a wide spectrum, derived from imidazole-dioxolane, which exerts a fungistatic and sporicidal effect on dermatophytes in dogs.

Ketoconazole widely inhibits the cytochrome P450 system. Ketoconazole modifies the permeability of membranes of fungi, and inhibit specifically the synthesis of ergosterole, which is an essential component of the cellular membrane of fungi, principally by inhibiting the enzyme cytochrome P450 14-alpha-demethylase (P45014DM).

Ketoconazole has anti-androgen and anti-glucocorticoid effects; it inhibits the conversion of cholesterol to steroid hormones such as testosterone and cortisol. It produces this effect through inhibition of cytochrome P450 enzymes involved in the synthesis.

Through inhibition of CYP3A4, metabolism of many drugs is decreased and their in-vivo bioavailability increased.

Ketoconazole inhibits p-glycoprotein efflux pumps and may increase the oral absorption and tissue distribution of other medicines, e.g. prednisolone.

After oral administration, peak plasma levels of 22-49 µg/ml (mean 35 µg/ml) are obtained within 1.5-4.0 hours (mean 2.9 hours).

Ketoconazole absorption is enhanced in an acidic environment and drugs that raise gastric pH may lessen absorption. High levels of the drug are found in the liver, adrenals, and pituitary gland, while more moderate levels are found in the kidneys, lungs, bladder, bone marrow, and myocardium. At usual doses (10 mg/kg), drug levels attained are probably inadequate in the brain, testis, and eyes to treat most infections; higher dosages are required. It crosses the placenta (in rats) and is excreted into milk.

Ketoconazole is 84-99% bound to the albumin fraction of plasma proteins. Ketoconazole is metabolised by the liver into several inactive metabolites. It is excreted predominantly into bile and to a lesser extent into urine. The terminal elimination half-life ranged between 3 and 9 hours (mean 4.6 hours).