Mawby Dianne I, Whittemore Jacqueline C, Fowler Leanne E, Papich Mark G
J Am Vet Med Assoc. 2018 Jan 15;252(2):195-200. doi: 10.2460/javma.252.2.195.
OBJECTIVE To compare absorption characteristics of orally administered compounded itraconazole capsules and suspension with those of reference (brand-name) formulations in healthy cats. DESIGN Randomized crossover study. ANIMALS 8 healthy adult cats. PROCEDURES After 12 hours of food withholding, cats received 50 mg of itraconazole (reference capsule, reference solution, compounded capsule, and compounded suspension) in a randomized crossover design, with a 21-day washout period. Capsules were administered with a small meal. Blood samples were collected at predetermined intervals for high-pressure liquid chromatography analysis of plasma itraconazole concentrations. Area under the concentration-time curve, maximum concentration, and terminal half-life of itraconazole were determined and compared among formulations. RESULTS 7 cats completed the study. Mean half-life of itraconazole in reference formulations was 18 to 26 hours. Absorption of the reference solution was 3 times that of the reference capsule. Compounded formulations were absorbed poorly and inconsistently. Complete pharmacokinetic results for the compounded capsule were obtained for only 3 of 6 cats and for the compounded suspension for only 1 of 5 cats, precluding bioequivalence analysis. Relative absorption of compounded formulations was only 2% to 8% of reference formulation values. CONCLUSIONS AND CLINICAL RELEVANCE Compounded oral formulations of itraconazole should not be used for cats because of poor absorption. The differences in absorption between the 2 reference formulations suggested that doses required to meet human target serum concentrations in cats are markedly different (capsules, 12.5 mg/kg [5.7 mg/lb], q 24 h, with food; solution, 4 mg/kg [1.8 mg/lb], q 24 h, without food).
目的 比较口服复方伊曲康唑胶囊和混悬液与对照（品牌名）制剂在健康猫体内的吸收特性。 设计 随机交叉研究。 动物 8只健康成年猫。 方法 在禁食12小时后，猫以随机交叉设计接受50毫克伊曲康唑（对照胶囊、对照溶液、复方胶囊和复方混悬液），洗脱期为21天。胶囊与少量食物一起给药。在预定时间间隔采集血样，用于高压液相色谱分析血浆伊曲康唑浓度。测定并比较各制剂的浓度-时间曲线下面积、最大浓度和伊曲康唑的末端半衰期。 结果 7只猫完成了研究。对照制剂中伊曲康唑的平均半衰期为18至26小时。对照溶液的吸收是对照胶囊的3倍。复方制剂吸收差且不一致。6只猫中只有3只获得了复方胶囊完整的药代动力学结果，5只猫中只有1只获得了复方混悬液完整的药代动力学结果，因此无法进行生物等效性分析。复方制剂的相对吸收仅为对照制剂值的2%至8%。 结论及临床意义 由于吸收差，不应将复方口服伊曲康唑制剂用于猫。两种对照制剂之间的吸收差异表明，猫达到人类目标血清浓度所需的剂量明显不同（胶囊，12.5毫克/千克[5.7毫克/磅]，每24小时一次，与食物同服；溶液，4毫克/千克[1.8毫克/磅]，每24小时一次，不与食物同服）。
