Smith Joseph A, Papich Mark G, Russell Gregg, Mitchell Mark A
Fort Wayne Children's Zoo, 3411 Sherman Boulevard, Fort Wayne, Indiana 46808, USA.
J Zoo Wildl Med. 2010 Sep;41(3):487-95. doi: 10.1638/2010-0019.1.
Itraconazole is used to treat and prevent aspergillosis in captive penguin colonies. Although commercial formulations of itraconazole are available, compounding is sometimes performed to decrease cost or to provide a different concentration of the drug. Using a two-way crossover design, the pharmacokinetics of both a commercially available oral itraconazole solution and a compounded oral itraconazole solution were compared in six black-footed penguins (Spheniscus demersus). Each itraconazole formulation was administered orally in frozen-thawed capelin at 7 mg/kg. Plasma itraconazole concentrations at time 0 (pretreatment), 20 and 40 min post-drug administration, and 1, 2, 4, 6, 8, and 12 hr post-drug administration were determined using reverse-phase high-performance liquid chromatography. Drug concentrations were analyzed using standard pharmacokinetic methods. Plasma clearance of the commercial itraconazole solution was more rapid than the clearance published for other species, possibly warranting more frequent dosing in black-footed penguins. Absorption of itraconazole, as determined by peak concentration and area under the curve, was significantly higher for the commercial formulation when compared to the compounded formulation, likely as a result of the presence of cyclodextrin, a carrier compound shown to improve oral absorption, in the commercial formulation. Extrapolating dosing regimens for compounded itraconazole formulations from regimens determined for commercial formulations warrants caution as a result of the significant differences in pharmacokinetics.
伊曲康唑用于治疗和预防圈养企鹅群体中的曲霉病。尽管有伊曲康唑的商业制剂，但有时会进行配制以降低成本或提供不同浓度的药物。采用双向交叉设计，在六只非洲企鹅（斑嘴环企鹅）中比较了市售口服伊曲康唑溶液和配制口服伊曲康唑溶液的药代动力学。每种伊曲康唑制剂均以7 mg/kg的剂量口服给予冻融毛鳞鱼。使用反相高效液相色谱法测定给药前（0时）、给药后20和40分钟以及给药后1、2、4、6、8和12小时的血浆伊曲康唑浓度。使用标准药代动力学方法分析药物浓度。市售伊曲康唑溶液的血浆清除率比其他物种公布的清除率更快，这可能需要对非洲企鹅更频繁地给药。与配制制剂相比，市售制剂的伊曲康唑吸收（通过峰浓度和曲线下面积确定）显著更高，这可能是由于市售制剂中存在环糊精，一种已证明可改善口服吸收的载体化合物。由于药代动力学存在显著差异，从市售制剂确定的给药方案推断配制伊曲康唑制剂的给药方案时需谨慎。
