pharmacokinetics of the cyclosporine-ketoconazole interaction in dogs

Adverse effects of ketoconazole in dogs – a ..
Although ketoconazole has been used extensively in dogs for the treatment of various fungal infections, information about adverse effects is mainly anecdotal. Common adverse effects in humans include dose‐dependant anorexia, nausea and vomiting, allergic rashes and pruritus. Drug‐induced hepatitis is very rare, but potentially fatal. The aim of this study was to evaluate the type and frequency of adverse effects associated with ketoconazole therapy in dogs treated for skin diseases and any possible influence of dosage, duration of therapy, signalment or concurrent medication. The medical records of 632 dogs treated with ketoconazole (2.6–33.4 mg/kg) were reviewed. Adverse effects occurred in 14.6% (92 dogs) and included vomiting (7.1%), anorexia (4.9%), lethargy (1.9%), diarrhea (1.1%), pruritus (0.6%), erythema (0.3%) and other adverse effects (2.5%). Of the dogs with other adverse effects, four of 16 (25%) were ataxic and three of these received concurrent ivermectin. Adverse effects were significantly more often recorded in dogs concurrently treated with ciclosporin (P = 0.034) or ivermectin (P = 0.007). Increased liver enzyme levels were reported rarely, and icterus was not seen in any of the dogs. However, monitoring liver enzymes during therapy is recommended, although this might not necessarily prevent severe idiosyncratic hepatotoxicity.
Plasma drug levels of DIO-902 and Racemic Ketoconazole in Dogs following Single and Repeat Oral Dosing
Ketoconazole treatment resulted in a significant decrease in the intrinsic clearance of CYA in dogs. A study in human liver microsomal incubates has shown that ketoconazole inhibits the metabolism of CYA. A Michaelis-Menten plot of the data indicated a mixed type of inhibition (Mauer, 1985). Pretreatment with ketoconazole probably inhibited the oxidative enzymes responsible for CYA metabolism which in turn accounts for the observed decrease in its intrinsic clearance in the five dogs. Lack of any significant difference in the amount of parent CYA and various metabolites excreted in the bile/urine mixture during the two different phases indicates no selective inhibition of any specific pathways of CYA elimination by ketoconazole in dogs. Earlier studies have suggested that ketoconazole is a potent and specific inhibitor of N-demethylase activity in humans and animals (; ; ). Pharmacokinetics of the cyclosporine-ketoconazole interaction in dogs.Pharmacokinetics of the cyclosporine-ketoconazole interaction in dogsKetoconazole Solution In Dogs -
Although ketoconazole has been used extensively in dogs for the treatment of various fungal infections, information about adverse effects is mainly anecdotal. Common adverse effects in humans include dose-dependant anorexia, nausea and vomiting, allergic rashes and pruritus. Drug-induced hepatitis is very rare, but potentially fatal. The aim of this study was to evaluate the type and frequency of adverse effects associated with ketoconazole therapy in dogs treated for skin diseases and any possible influence of dosage, duration of therapy, signalment or concurrent medication. The medical records of 632 dogs treated with ketoconazole (2.6-33.4 mg/kg) were reviewed. Adverse effects occurred in 14.6% (92 dogs) and included vomiting (7.1%), anorexia (4.9%), lethargy (1.9%), diarrhea (1.1%), pruritus (0.6%), erythema (0.3%) and other adverse effects (2.5%). Of the dogs with other adverse effects, four of 16 (25%) were ataxic and three of these received concurrent ivermectin. Adverse effects were significantly more often recorded in dogs concurrently treated with ciclosporin (P = 0.034) or ivermectin (P = 0.007). Increased liver enzyme levels were reported rarely, and icterus was not seen in any of the dogs. However, monitoring liver enzymes during therapy is recommended, although this might not necessarily prevent severe idiosyncratic hepatotoxicity.[0019] Figure 4 shows the effect of prior exposure to ketoconazole on the pharmacokinetic profile of racemic ketoconazole in dogs. The pharmacokinetic profile of racemic ketoconazole is clearly altered by prior exposure to racemic ketoconazole. The concentration of racemic ketoconazole in the plasma of dogs that were dosed with racemic ketoconazole daily for 28 days (in two different forms: in suspension in olive oil and in a solid tablet form) is significantly greater than the concentration of racemic ketoconazole in the plasma of dogs that were treated only once.There are many different ketoconazole drug interactions in dogs, so it is very important to know the animal’s medical history before it is prescribed. The veterinarian should be informed about any medical conditions that the dog has had in the past, and other medications that have been given. Ketoconazole should not be taken by dogs that have had problems with blood clotting, stomach ulcers, or . In addition, dogs that have had allergic reactions to similar medications, such as other anti-fungal drugs, should not be give this medication. It cannot be given to pregnant dogs, as it will result in the death of the fetus(es). [0021] Figure 6 shows the effect of prior exposure to the 2S,4R enantiomer of ketoconazole on the pharmacokinetic profile of the 2S,4R enantiomer of ketoconazole in dogs. The pharmacokinetic profile of the 2S,4R enantiomer of ketoconazole is not altered by prior exposure to the 2S,4R enantiomer of ketoconazole. The concentration of the 2S,4R enantiomer of ketoconazole in the plasma of dogs that were dosed either once with the 2S,4R enantiomer or were dosed daily for 28 days is not increased in the dogs treated for 28 days as compared to dogs treated only once.