Therapeutic drug monitoring of itraconazole in treatment of blastomycosis in dogs.

Abstract

BACKGROUND: Itraconazole is a widely used treatment for blastomycosis in dogs but serum drug concentrations vary widely between individuals. HYPOTHESIS/OBJECTIVES: Establish a protocol for therapeutic drug monitoring of itraconazole in dogs with blastomycosis. ANIMALS: Fourteen dogs with blastomycosis. METHODS: Single-arm, prospective study. The initial dosage of itraconazole was 5&#xa0;mg/kg/day. Therapeutic drug monitoring was performed after 2 weeks and then monthly until clinical and antigenic remission. Itraconazole dosages were adjusted to maintain trough serum concentrations within the target range (2-7&#xa0;&#x3bc;g/mL) using a standardized equation. RESULTS: Twelve of 14 dogs required at least 1 dosage adjustment and 9 dogs required additional adjustments even after target concentrations were initially achieved. Dosage changes tended to occur at sequential visits, often consisting of a dosage increase followed by a dosage decrease at the next visit, or vice versa. No correlation was found between itraconazole dosage and serum concentration (r&#xa0;=&#xa0;0.080, P&#xa0;=&#xa0;.43). Dogs were treated for a median of 7.9&#xa0;months (range, 2.6-9.9). Median itraconazole dosage at disease remission (2.8&#xa0;mg/kg/day; range, 0.9-5.0) was significantly lower than the initial dosage (4.9&#xa0;mg/kg/day; range, 4.0-5.4; P&#xa0;<&#xa0;.001). All dogs successfully achieved remission of blastomycosis and only one occurrence of antigenic relapse occurred. CONCLUSIONS AND CLINICAL IMPORTANCE: Most dogs with blastomycosis require dosage adjustments to maintain itraconazole concentrations in the target range. Repeat serum drug concentrations should be measured after dosage adjustments to ensure target concentrations are reached. Although 5&#xa0;mg/kg/day is an appropriate initial dosage, the itraconazole dosage needed to maintain target serum concentrations appears to decrease over time.