单次口服普伐他汀超过靶血药浓度,在荷兰小鹦鹉体内表现出良好的药代动力学特征。

IF 1.4 3区 农林科学 Q2 VETERINARY SCIENCES
Marina R Liles, David Sanchez-Migallon Guzman, Heather Knych, Hugues Beaufrère
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引用次数: 0

摘要

目的:评价单次口服普伐他汀对大鼠血药浓度及药动学的影响。方法:在20、40和80 mg/kg的单次口服剂量下进行初步研究。根据初步研究的结果,14只成年鹦鹉(7只雄性和7只雌性)通过灌胃使用复合普伐他汀口服混悬液给予40 mg/kg剂量。采用平衡不完全区组设计,在给药后0.5 ~ 12h的7个不同时间点采集血样,每只鸟3份血样,每个时间点6个重复。采用LC-MS-MS法测定普伐他汀血药浓度。采用区室分析进行药代动力学分析。结果:达到最大浓度所需时间为2小时,最大血药浓度为669.9 ng/mL,终末半衰期为3小时。个体间差异很大,1只鹦鹉在所有样本点都有极高水平的普伐他汀,因此被排除在分析之外。结论:单次口服40 mg/kg的普伐他汀剂量超过了人类的血浆浓度(45至55 ng/mL)。临床相关性:起始剂量为40mg /kg, PO,每24小时或更低,在多剂量药代动力学研究、评估降血脂效果的功效研究以及可能在饮用水中给药的进一步研究中,有可能有益于治疗脂质紊乱的cockatiels。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Single oral dose of pravastatin exceeded target plasma concentrations and displayed a favorable pharmacokinetic profile in cockatiels (Nymphicus hollandicus).

Objective: To evaluate the plasma concentrations and determine the pharmacokinetic profile of pravastatin after administration of a single oral dose in cockatiels.

Methods: A pilot study was performed at single oral doses of 20, 40, and 80 mg/kg. Based on the results of the pilot study, 14 adult cockatiels (7 male and 7 female) were administered a 40-mg/kg dose using a compounded oral suspension of pravastatin via oral gavage. Blood samples were collected at 7 different time points from 0.5 to 12 hours after administration in a balanced incomplete block design, with 3 blood samples/bird and 6 replicates/time point. Plasma concentrations of pravastatin were determined via LC-MS-MS. Pharmacokinetic analysis was performed using compartmental analysis.

Results: The estimated time to maximum concentration, maximum plasma concentration, and terminal half-life were 2 hours, 669.9 ng/mL, and 3 hours, respectively. There was high interindividual variability, and 1 cockatiel had extremely high levels of pravastatin through all sample points and was excluded from the analysis.

Conclusions: A single oral dose of 40 mg/kg of pravastatin administered to cockatiels exceeded plasma concentrations that would be considered therapeutic in humans (45 to 55 ng/mL).

Clinical relevance: A starting dose of 40 mg/kg, PO, every 24 hours or lower has the potential of being beneficial in the treatment of cockatiels with lipid disorders pending further investigations with multidose pharmacokinetic studies, efficacy studies evaluating hypolipidemic effect, and its possible administration in drinking water.

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来源期刊
CiteScore
1.70
自引率
10.00%
发文量
186
审稿时长
3 months
期刊介绍: The American Journal of Veterinary Research supports the collaborative exchange of information between researchers and clinicians by publishing novel research findings that bridge the gulf between basic research and clinical practice or that help to translate laboratory research and preclinical studies to the development of clinical trials and clinical practice. The journal welcomes submission of high-quality original studies and review articles in a wide range of scientific fields, including anatomy, anesthesiology, animal welfare, behavior, epidemiology, genetics, heredity, infectious disease, molecular biology, oncology, pharmacology, pathogenic mechanisms, physiology, surgery, theriogenology, toxicology, and vaccinology. Species of interest include production animals, companion animals, equids, exotic animals, birds, reptiles, and wild and marine animals. Reports of laboratory animal studies and studies involving the use of animals as experimental models of human diseases are considered only when the study results are of demonstrable benefit to the species used in the research or to another species of veterinary interest. Other fields of interest or animals species are not necessarily excluded from consideration, but such reports must focus on novel research findings. Submitted papers must make an original and substantial contribution to the veterinary medicine knowledge base; preliminary studies are not appropriate.
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