Frazier D L, Price G S
Department of Comparative Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071, USA.
J Vet Intern Med. 1998 Jul-Aug;12(4):272-8. doi: 10.1111/j.1939-1676.1998.tb02122.x.
Anticancer drug dosages that specify the maximum dose and minimum dosing interval that are tolerated in a population of dogs are commonly recommended. Because the differences between the effective and toxic doses of most cancer chemotherapeutics is slight, it is important to achieve therapeutic concentrations in tumor tissues at the same time that concentrations in nontarget tissues are minimized. In order to determine the dosage regimen that will most likely accomplish these goals, similar drug concentrations must be achieved in all patients dosed according to a specific regimen. Dosing based on body surface area (BSA) is generally used in an effort to normalize drug concentrations. This is because it is well recognized that measures of many physiologic parameters that are responsible for drug disposition, including renal function and energy expenditure, can be normalized by use of BSA. However, there is substantial evidence that drug disposition is not always proportional to BSA. Differences in distribution, metabolism, and excretion pathways may preclude dose extrapolation among species or among individuals within a species based on BSA. Moreover, genetic differences in drug metabolism are well recognized in humans and in laboratory animals, and it is likely that similar differences exist among breeds of dogs. A review of the pharmacokinetic disposition of several cancer chemotherapeutics suggests that studies are needed to determine the most effective method to achieve equivalent anticancer drug concentrations in diverse veterinary patients.
通常推荐使用抗癌药物剂量，该剂量规定了犬类群体中可耐受的最大剂量和最小给药间隔。由于大多数癌症化疗药物的有效剂量和毒性剂量之间差异很小，因此在使非靶组织中的浓度最小化的同时，在肿瘤组织中达到治疗浓度非常重要。为了确定最有可能实现这些目标的给药方案，按照特定方案给药的所有患者必须达到相似的药物浓度。基于体表面积（BSA）给药通常用于使药物浓度标准化。这是因为人们普遍认识到，包括肾功能和能量消耗在内的许多负责药物处置的生理参数的测量值可以通过使用BSA进行标准化。然而，有大量证据表明药物处置并不总是与BSA成正比。分布、代谢和排泄途径的差异可能会妨碍基于BSA在物种之间或同一物种内的个体之间进行剂量推算。此外，药物代谢的遗传差异在人类和实验动物中已得到充分认识，犬类品种之间可能也存在类似差异。对几种癌症化疗药物的药代动力学处置的综述表明，需要进行研究以确定在不同兽医患者中实现等效抗癌药物浓度的最有效方法。
