Body surface area as a determinant of pharmacokinetics and drug dosing
Body surface area as a determinant of pharmacokinetics and drug dosing
复制标题
DOI：
10.1023/a:1010639201787
复制
发表时间：
2001-05-01
影响因子：
3.4
通讯作者：
Ratain, MJ
中科院分区：
文献类型：
--
作者：
Sawyer, M;Ratain, MJ
体表面积（BSA）被引入到医学肿瘤学中，以便从临床前动物毒理学数据中推导出抗癌药物I期研究的安全起始剂量。然而，尚不清楚为什么将BSA给药扩展到常规给药的抗肿瘤药物。存在几个公式来估计BSA，但DuBois和DuBois推导的公式是成人医学肿瘤学中使用的公式。该公式仅基于9名患者的数据得出;随后验证该公式的尝试发现DuBois公式高估或低估了实际测定的BSA。虽然心输出量确实与BSA相关，但BSA与药物代谢和处置相关的其他生理指标（如肾功能和肝功能）之间的关系很弱或不存在。此外，仅研究了表阿霉素、依托泊苷和卡铂，以确定BSA给药是否会降低患者间变异性，发现这些药物的药代动力学与BSA之间均无显著关系。新药物的未来临床试验不应假定基于BSA的剂量会降低患者间的变异性。研究应检查BSA在初始I期研究中给药新化疗药物中的作用（如有）。
Body surface area (BSA) was introduced into medical oncology in order to derive a safe starting dose for phase I studies of anticancer drugs from preclinical animal toxicology data. It is not clear however, as to why dosing by BSA was extended to the routine dosing of antineoplastic agents. Several formulas exist to estimate BSA, but the formula derived by DuBois and DuBois is the one used in adult medical oncology. This formula was derived based on data from only nine patients; subsequent attempts to validate the formula have found the DuBois formula to either over or underestimate the actual determined BSA. While cardiac output does correlate with BSA, the relationship between BSA and other physiologic measures relevant for drug metabolism and disposition, such as, renal and hepatic function, is weak or nonexistent. Further only epirubicin, etoposide, and carboplatin have been studied to determine if dosing by BSA would reduce interpatient variability, and none of these drugs were found to have significant relationships between their pharmacokinetics and BSA. Future clinical trials of new agents should not presume that dosing based on BSA reduces interpatient variability. Studies should examine the role, if any, BSA has in dosing new chemotherapeutic agents in initial phase I studies.