The effects of formulation on the pharmacokinetics of itraconazole and amiodarone in dogs after oral administration of a combination product, commercial products, and compounded products

IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY
Robert P. Hunter, Roy Madigan
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引用次数: 0

Abstract

This study evaluated four different formulations of itraconazole and amiodarone. Formulation 1 was Vida's combination tablet containing both active pharmaceutical ingredients (APIs). Formulation 2 was separate, commercially available human generic capsules and tablets of itraconazole and amiodarone, respectively. Formulation 3 was separate, compounded suspensions of itraconazole and amiodarone. Formulation 4 was a compounded chewable tablet of itraconazole. Eight female dogs were dosed with 5 mg/kg of itraconazole and 15 mg/kg amiodarone (except for formulation 4, which only received 5 mg/kg itraconazole) once weekly for 4 weeks using a modified Latin Square design, ensuring that all dogs received all formulations with a 7-day washout between treatments. Animals were fasted overnight prior to each dose administration, with food returned to all animals 4 h post-dose. Blood samples (3 mL) were collected pre-treatment (0) and at appropriate time points over 72 h after each dose for a total of 14 samples per dog per treatment. There was high variability in the serum concentration data within treatment groups for itraconazole. The compounded suspensions were difficult to dose due to the nature of the formulations. The volumes dosed were accurate and consistent, but the suspension was thin and settled immediately when shaking was stopped for both itraconazole and amiodarone. All serum samples following itraconazole chewable tablet administration were not detectable or just above itraconazole's LOQ and thus did not allow for pharmacokinetic determination.

口服联合产品、商业产品和复合产品后,制剂对伊曲康唑和胺碘酮在狗体内的药代动力学的影响。
本研究评估了伊曲康唑和胺碘酮的四种不同制剂。制剂1是Vida的含有两种活性药物成分(API)的组合片剂。制剂2分别是伊曲康唑和胺碘酮的单独的、市售的人非专利胶囊和片剂。制剂3是伊曲康唑和胺碘酮的单独的复合悬浮液。制剂4是伊曲康唑的复合咀嚼片。8只雌性狗服用5 mg/kg伊曲康唑和15 mg/kg胺碘酮(配方4除外,仅接受5 mg/kg伊曲康唑),每周一次,共4次 使用改良的Latin Square设计,确保所有狗在两次治疗之间接受7天冲洗的所有配方。动物在每次给药前禁食过夜,并将食物退还给所有动物4 h给药后。血样(3 mL)在预处理(0)和适当的时间点收集超过72 每次给药后h,每只狗每次治疗总共14个样本。伊曲康唑治疗组的血清浓度数据具有高度变异性。由于配方的性质,复合悬浮液很难给药。给药的体积准确且一致,但当伊曲康唑和胺碘酮停止振荡时,悬浮液很薄并立即沉淀。伊曲康唑咀嚼片给药后的所有血清样本均未检测到或略高于伊曲康唑的LOQ,因此不允许进行药代动力学测定。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.10
自引率
15.40%
发文量
69
审稿时长
8-16 weeks
期刊介绍: The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.
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