Veterinary Medicine - January 2008 - (Page 44)

Systemic antifungals PEER-REVIEWED that of the parent compound. Itraconazole is variably absorbed after oral administration in dogs and cats.20,21 In dogs, itraconazole absorption is above 90% when capsules are administered with food compared with about 40% absorption in fasted patients. In fasted cats, itraconazole solution is about 70% absorbed.21 Itraconazole is primarily eliminated by hepatic metabolism and biliary secretion, with less than 1% of the drug eliminated by renal mechanisms.20 The half-life in dogs and cats is 28 to 30 hours after a single dose. The half-life increases with multiple doses. Itraconazole is highly lipophilic, so concentrations in tissues persist longer than plasma concentrations. As a result of itraconazole accumulation in tissue such as the stratum corneum, pulse dosing has been effective in treating Malassezia dermatitis in dogs (5 mg/kg orally once a day for two days, repeated weekly for three weeks) and dermatophyte infections in cats (5 to 10 mg/kg orally once a day for seven days, then alternating one week on, one week off until a cure is achieved).22 However, systemic treatment with itraconazole as a sole treatment for Malassezia otitis has resulted in poor responses, and adjunctive treatments, such as topical medications, are suggested.22 Itraconazole inhibits CYP-mediated drug metabolism similar to ketoconazole but to less of an extent.25 However drugdrug interactions with itraconazole may include those listed for ketoconazole. Itraconazole, similar to ketoconazole, is also a Pgp ef ux pump inhibitor.11 Itraconazole absorption is decreased when the drug is administered with gastric acid suppression treatment, so it should not be administered concurrently. Itraconazole has a negative inotropic effect, which may lead to congestive heart failure in patients with impaired ventricular function.16 Long-term administration of phenobarbital increases itraconazole metabolism and may require increased dosages to maintain similar ef cacy. time to maximum plasma concentration) after 10 mg/kg was administered orally. In contrast to itraconazole and ketoconazole, uconazole is well-absorbed in the fasted state.16 Greater than 70% of the dose was eliminated in the urine of dogs as unchanged drug.28 The pharmacokinetics of uconazole in cats is similar to that in dogs: a CMAX of 12.9 g/ml at a TMAX of 1.3 hours with complete absorption after oral administration (10.8 mg/kg) and a terminal half-life of about 24 hours.29 Fluconazole penetrates the cerebrospinal uid, aqueous humor, and bronchial epithelial uid well.29 Drug interactions and adverse effects Fluconazole is generally well-tolerated, but adverse effects similar to those of the other azoles can occur,1 including nausea, anorexia, and vomiting. Severe hepatic reactions have been reported in people, so serum hepatic enzyme activities should be routinely monitored before and during long-term therapy.16 Rare hematologic adverse effects including anemia, thrombocytopenia, leukopenia, and neutropenia have been reported in people. Fluconazole use during pregnancy is generally not recommended, as there are con icting data on its mutagenic or teratogenic potential.16,30 Fluconazole is excreted in milk, so it is not recommended to be administered to lactating animals.16 Fluconazole absorption is not affected by decreased gastric acidity, so concurrent administration with gastric acid suppression treatment is not expected to affect absorption.16 Fluconazole exhibits a slightly different CYP inhibitory pro le than ketoconazole and itraconazole, so some differences in drug-drug interactions are expected. In people, the metabolism of cyclosporine, buspirone, warfarin, quinidine, and some benzodiazepines has been decreased when they are concurrently administered with uconazole.16 FLUCONAZOLE Fluconazole is available as tablets (50, 100, 150, and 200 mg) and as a 10-mg/ml suspension. The typical cost of uconazole for a 44-lb dog (10 mg/kg orally once a day) is about 50¢/day. Potential indications Fluconazole has similar antifungal activity to itraconazole with a few notable exceptions. Typically, Aspergillus and Microsporum species are resistant to uconazole.26 Malassezia species are less sensitive to uconazole than to other azoles.27 Leishmania species may be more sensitive to uconazole than to itraconazole, although extensive ef cacy studies are lacking.17 Fluconazole is the treatment of choice for Cryptococcus species CNS infections because of the high drug concentrations achieved in the CNS.16 Drug interactions and adverse effects Itraconazole appears to be better tolerated than ketoconazole in dogs and cats. Itraconazole can result in nausea, vomiting, and anorexia, but these signs may occur less frequently and appear to be dose-dependent.23 Hepatotoxicosis may occur in as many as 10% of dogs receiving long-term treatment with itraconazole.23 As with ketoconazole, slight increases in liver enzyme activities can occur with itraconazole administration but are not indicative of hepatotoxicosis. The increases in liver enzyme activities appear to be correlated with increasing itraconazole plasma concentrations and dosages.1,23 In contrast to ketoconazole, itraconazole has minimal effects on cortisol and testosterone concentrations.24 Pharmacokinetics In contrast to the other antifungals, uconazole exhibits low plasma protein binding (about 11%) in all species evaluated.28 Limited studies have been done on the pharmacokinetics of uconazole in dogs. In a study evaluating two dogs, uconazole was completely absorbed after oral administration with a 15-hour half-life. The maximum plasma concentration (CMAX) achieved in dogs was about 10 g/ml at about four hours (TMAX; the VORICONAZOLE Voriconazole is a uconazole derivative, but it has a higher intrinsic activity against many fungal organisms. Vori- 44 January 2008 VETERINARY MEDICINE

Table of Contents Feed for the Digital Edition of Veterinary Medicine - January 2008

Veterinary Medicine - January 2008 Contents Digital Extra Letters Toxicology Brief Idea Exchange A Challenging Case: Phimosis in a Young Adult Dog The Indications and Technique for Continuous Ambulatory Electrocardiographic Recording in Dogs A Review of Selected Systemic Antifungal Drugs for Use in Dogs and Cats CE Form Advertiser Index Marketplace/Classifieds Mind Over Miller

Veterinary Medicine - January 2008

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