Voisin E M, Ruthsatz M, Collins J M, Hoyle P C
U.S. Food and Drug Administration, Division of Antiviral Drug Products, Rockville, MD 20857.
Regul Toxicol Pharmacol. 1990 Oct;12(2):107-16. doi: 10.1016/s0273-2300(05)80052-2.
Different methods for converting the dose-related toxicity of drugs from animals to humans are reviewed. Each method is analyzed with respect to its utility and limitations. Linear extrapolations from animals to humans based on body weight equivalence are shown to be inaccurate unless species-specific conversion factors are used. Extrapolations based on surface area equivalence are more accurate, do not require conversion factors, and may be used when pharmacokinetic data are not available. Ultimately, interspecies conversions are most reliable when pharmacokinetic data are available, assuming that toxic responses are comparable among species for similar blood levels. Two pharmacokinetic-based approaches may be used: direct use of plasma concentration or area under the concentration-time curve (AUC) and physiologically based pharmacokinetic (PBPK) models.
本文综述了将药物剂量相关毒性从动物转换至人类的不同方法。针对每种方法的实用性和局限性进行了分析。结果表明，基于体重等效性从动物线性外推至人类是不准确的，除非使用物种特异性转换因子。基于体表面积等效性的外推更为准确，不需要转换因子，并且在没有药代动力学数据时也可使用。最终，当有药代动力学数据时，种间转换最为可靠，前提是相似血药水平下不同物种的毒性反应具有可比性。可采用两种基于药代动力学的方法：直接使用血浆浓度或浓度-时间曲线下面积（AUC）以及基于生理的药代动力学（PBPK）模型。
