Eiseman Julie L, Sciullo Michael, Wang Hong, Beumer Jan H, Horn Charles C
1 Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, USA.
2 Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, USA.
Lab Anim. 2017 Oct;51(5):534-537. doi: 10.1177/0023677217695851. Epub 2017 Feb 26.
Several cancer chemotherapies cause nausea and vomiting, which can be dose-limiting. Musk shrews are used as preclinical models for chemotherapy-induced emesis and for antiemetic effectiveness. Unlike rats and mice, shrews possess a vomiting reflex and demonstrate an emetic profile similar to humans, including acute and delayed phases. As with most animals, dosing of shrews is based on body weight, while translation of such doses to clinically equivalent exposure requires doses based on body surface area. In the current study body surface area in musk shrews was directly assessed to determine the Meeh constant (K) conversion factor (female = 9.97, male = 9.10), allowing estimation of body surface area based on body weight. These parameters can be used to determine dosing strategies for shrew studies that model human drug exposures, particularly for investigating the emetic liability of cancer chemotherapeutic agents.
几种癌症化疗药物会引起恶心和呕吐,这可能会限制剂量。麝鼩被用作化疗引起的呕吐和止吐效果的临床前模型。与大鼠和小鼠不同,麝鼩具有呕吐反射,并且表现出与人类相似的呕吐特征,包括急性期和延迟期。与大多数动物一样,给麝鼩给药是基于体重,而将这些剂量转换为临床上等效的暴露量则需要基于体表面积的剂量。在当前研究中,直接评估了麝鼩的体表面积以确定米氏常数(K)转换因子(雌性 = 9.97,雄性 = 9.10),从而能够根据体重估算体表面积。这些参数可用于确定模拟人类药物暴露的麝鼩研究的给药策略,特别是用于研究癌症化疗药物的致吐倾向。