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Clinical pharmacokinetics and outcomes of oral fluconazole therapy in dogs and cats with naturally occurring fungal disease.
Journal of Veterinary Pharmacology and Therapeutics ( IF 1.5 ) Pub Date : 2020-07-12 , DOI: 10.1111/jvp.12888
Kate KuKanich 1 , Butch KuKanich 2 , Zhoumeng Lin 2 , Amy J Rankin 1 , Andrew S Hanzlicek 3 , Jean-Sebastien Palerme 4 , Jonathan Bach 5 , Audrey K Cook 6 , Amy Juracek 1 , Hyun Joo 2
Affiliation  

This multi‐institutional study was designed to determine the clinical pharmacokinetics of fluconazole and outcomes in client‐owned dogs (n = 37) and cats (n = 35) with fungal disease. Fluconazole serum concentrations were measured. Pharmacokinetic analysis was limited to animals at steady state (≥72 hr of treatment). The mean (range) body weight in 31 dogs was 25.6 (2.8–58.2) kg and in 31 cats was 3.9 (2.4–6.1) kg included in pharmacokinetic analyses. The dose, average steady‐state serum concentrations (CSS), and oral clearance in dogs were 14.2 (4.5–21.3) mg/kg/d, 26.8 (3.8–61.5) µg/mL, and 0.63 ml min−1 kg−1, respectively, and in cats were 18.6 (8.2–40.0) mg/kg/d, 32.1 (1.9–103.5) µg/mL, and 0.61 ml min−1 kg−1, respectively. Random inter‐animal pharmacokinetic variability was high in both species. Two dogs had near twofold increases in serum fluconazole when generic formulations were changed, suggesting lack of bioequivalence. Median CSS for dogs and cats achieving clinical remission was 19.4 and 35.8 µg/ml, respectively. Starting oral doses of 10 mg/kg q12h in dogs and 50–100 mg total daily dose in cats are recommended to achieve median CSS associated with clinical remission. Due to the large pharmacokinetic variability, individualized dose adjustments based on CSS (therapeutic drug monitoring) and treatment failure should be considered.

中文翻译:

在患有自然真菌病的狗和猫中,口服氟康唑的临床药代动力学和疗效。

这项多机构研究旨在确定氟康唑的临床药代动力学以及在 患有真菌病的客户拥有的狗(n  = 37)和猫(n = 35)中的结果。测量氟康唑的血清浓度。药代动力学分析仅限于处于稳态(≥72小时治疗)的动物。包括在药代动力学分析中的31只狗的平均(范围)体重为25.6(2.8-58.2)kg,而31只猫的平均体重为3.9(2.4–6.1)kg。剂量,平均稳态血清浓度(C SS),并且在口服狗清除率14.2(4.5-21.3)毫克/公斤/ d,26.8(3.8-61.5)微克/毫升,和0.63毫升分钟-1 千克- 1和猫分别为18.6(8.2–40.0)mg / kg / d,32.1(1.9–103.5)µg / mL和0.61 ml-1  kg -1。两种动物的动物间药代动力学随机性均较高。更改通用配方后,两只狗的血清氟康唑含量增加了将近两倍,表明缺乏生物等效性。达到临床缓解的狗和猫的C SS中位数分别为19.4和35.8 µg / ml。建议在犬中每12h开始口服10 mg / kg的剂量,在猫中每日总剂量的50–100 mg,以实现与临床缓解相关的中位C SS。由于较大的药代动力学差异,应考虑基于C SS(治疗药物监测)和治疗失败进行个体化剂量调整。
更新日期:2020-07-12
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