USE OF BODY-SURFACE AREA TO CALCULATE CHEMOTHERAPEUTIC DRUG DOSE IN DOGS - II - LIMITATIONS IMPOSED BY PHARMACOKINETIC FACTORS

Anticancer drug dosages that specify the maximum dose and minimum dosi ng interval that are tolerated in a population of dogs are commonly re commended. Because the differences between the effective and toxic dos es of most cancer chemotherapeutics is slight, it is important to achi eve therapeutic concentrations in tumor tissues at the same time that concentrations in nontarget tissues are minimized. In order to determi ne the dosage regimen that will most likely accomplish these goals, si milar drug concentrations must be achieved in all patients dosed accor ding 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 param eters that are responsible for drug disposition, including renal funct ion and energy expenditure, can be normalized by use of BSA. However, there is substantial evidence that drug disposition is not always prop ortional to BSA. Differences in distribution, metabolism, and excretio n pathways may preclude dose extrapolation among species or among indi viduals within a species based on BSA. Moreover, genetic differences i n drug metabolism are well recognized in humans and in laboratory anim als, and it is likely that similar differences exist among breeds of d ogs. A review of the pharmacokinetic disposition of several cancer che motherapeutics suggests that studies are needed to determine the most effective method to achieve equivalent anticancer drug concentrations in diverse veterinary patients.