Maxwell L K, Jacobson E R
Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
J Vet Pharmacol Ther. 2008 Feb;31(1):9-17. doi: 10.1111/j.1365-2885.2007.00915.x.
When body size varies greatly, drug disposition can best be described as an allometric function of body weight. Therefore, the allometry of standard metabolic rate (SMR; 3/4 power) and body surface area (BSA; 2/3 power) have been advocated as surrogate markers for the prediction of key pharmacokinetic parameters. The goal of the present study was to examine the allometric basis of pharmacokinetic scaling within a species, green iguanas. Enrofloxacin was administered intravenously to 20 green iguanas (322-3824 g), and noncompartmental analysis was used to calculate standard pharmacokinetic parameters, which were log(10) transformed and regressed against log(10) body weight. The slopes of significant regressions were compared with the values of unity, 3/4, and 2/3. The slope of enrofloxacin total body clearance (Cl) was also compared with the slopes relating SMR and renal Cl of (99m)Tc-diethylenetriamine penta-acetic acid ((99m)DTPA) to body weight in iguanas. Enrofloxacin Cl depended allometrically on body weight with the power of 0.32. The slope of enrofloxacin Cl was significantly less than those of SMR, Cl of (99m)DTPA, and the 2/3 value. Therefore, the relationship between enrofloxacin Cl and body weight does not directly depend on the allometry of BSA, SMR, or renal Cl of (99m)DTPA in iguanas.
当体型差异很大时，药物处置最好被描述为体重的异速生长函数。因此，标准代谢率（SMR；3/4幂）和体表面积（BSA；2/3幂）的异速生长已被提倡作为预测关键药代动力学参数的替代指标。本研究的目的是检验一个物种——绿鬣蜥体内药代动力学标度的异速生长基础。将恩诺沙星静脉注射给20只绿鬣蜥（322 - 3824克），并使用非房室分析来计算标准药代动力学参数，将这些参数进行log(10)转换后与log(10)体重进行回归分析。将显著回归的斜率与1、3/4和2/3的值进行比较。还将恩诺沙星总体清除率（Cl）的斜率与绿鬣蜥中SMR以及（99m）锝 - 二乙三胺五乙酸（（99m）DTPA）的肾清除率与体重的关系斜率进行比较。恩诺沙星的Cl以0.32的幂次异速依赖于体重。恩诺沙星Cl的斜率显著小于SMR、（99m）DTPA的Cl以及2/3值的斜率。因此，在绿鬣蜥中，恩诺沙星Cl与体重之间的关系并不直接依赖于BSA、SMR或（99m）DTPA的肾清除率的异速生长关系。
