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
{"title":"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","authors":"Robert P. Hunter, Roy Madigan","doi":"10.1111/jvp.13411","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"47 2","pages":"65-72"},"PeriodicalIF":1.5000,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of veterinary pharmacology and therapeutics","FirstCategoryId":"97","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/jvp.13411","RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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.