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种间异速生长比例关系

Interspecies allometric scaling.

作者信息

Hunter Robert P

机构信息

Elanco Animal Health, a division of Eli Lilly, 2001 West Main Street, Greenfield, Indiana 46140, USA.

出版信息

Handb Exp Pharmacol. 2010(199):139-57. doi: 10.1007/978-3-642-10324-7_6.

Abstract

Lack of approved pharmaceutical agents and very limited pharmacokinetic data in the scientific literature for exotic, wildlife, and zoo species are a major issue for veterinarians treating these species. There are fewer than 15 compounds approved in the United States for zoo and wildlife species compared to nearly 300 drugs licensed for cattle. Zoo veterinarians are therefore required to extrapolate the use of approved agents (veterinary or human) to nonapproved species, often with little or no scientific basis to support drug or dose schedule selection. In general, species differences in drug absorption, metabolism, distribution, and excretion have been well documented for domestic species. However, there has been limited research to provide similar data for nondomestic species. Consequently, with the possible exception of pet bird species, there is little published information on the pharmacokinetic parameters of drugs in nondomestic species. Additionally, because of the commercial value of many zoo species, the traditional method of "trial and error" for drug and dose selection and related compliance issues is often inappropriate. There is an understandable concern, whereby the zoo veterinarian does not wish to be the first to administer an agent or formulation in an untested species. "One medicine" is a central concept in treating zoo species, in that vertebrate species are generally more similar than dissimilar. However, drug absorption can vary within as well as between species. Considering the anatomical differences between true monogastrics (canine and feline species), hind-gut fermentors (rodents, rabbits, horses, and elephants), fore-gut fermentors (Colobus monkeys and kangaroos), and ruminants (cattle, goats, sheep, and antelope), the potential for differences in pharmacokinetic profiles are marked. Moreover, there are potential differences between organisms in a single class. An example is the ability of several snake species to up- and down-regulate their digestive systems. This renders the time course of oral drug absorption dependent on both body temperature and time after feeding. Plasma protein binding may vary considerably between species and may also be temperature dependent. This is very significant when treating poikilothermic (reptiles, amphibians, and fish) species and when conducting pharmacokinetic studies with highly protein-bound drugs. The large body sizes of some zoo species create additional considerations for treatment with drugs and can place significant limitations on delivery of an effective drug dose.

摘要

缺乏经批准的药物制剂,且科学文献中有关外来物种、野生动物和动物园动物的药代动力学数据非常有限,这对治疗这些物种的兽医来说是一个主要问题。在美国,获批用于动物园动物和野生动物的化合物不到15种,而获批用于牛的药物有近300种。因此,动物园兽医常常需要将已获批药物(兽用或人用)外推至未获批物种使用,且往往几乎没有科学依据来支持药物或给药方案的选择。一般来说,家养动物在药物吸收、代谢、分布和排泄方面的种属差异已有充分记录。然而,针对非家养动物提供类似数据的研究却很有限。因此,除了宠物鸟类可能是个例外,关于非家养动物药物药代动力学参数的公开信息很少。此外,由于许多动物园动物具有商业价值,传统的“试错”方法来选择药物和剂量以及相关的合规问题往往并不合适。动物园兽医不愿率先在未经测试的物种中使用某种药物或制剂,这种担忧是可以理解的。“同一医学”是治疗动物园动物的核心概念,因为脊椎动物物种之间的相似性通常大于差异性。然而,药物吸收在种内和种间都可能存在差异。考虑到真单胃动物(犬科和猫科动物)、后肠发酵动物(啮齿动物、兔子、马和大象)、前肠发酵动物(疣猴和袋鼠)以及反刍动物(牛、山羊、绵羊和羚羊)之间的解剖学差异,药代动力学特征存在差异的可能性很大。此外,同一类生物之间也可能存在潜在差异。例如,几种蛇类能够上调和下调其消化系统。这使得口服药物吸收的时间过程既取决于体温,也取决于进食后的时间。种属之间的血浆蛋白结合可能有很大差异,并且也可能取决于温度。在治疗变温动物(爬行动物、两栖动物和鱼类)以及使用高蛋白结合药物进行药代动力学研究时,这一点非常重要。一些动物园动物体型巨大,这给药物治疗带来了更多需要考虑的因素,并且可能对有效药物剂量的给药造成重大限制。

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