Abstract：
Serial blood sampling from one animal is useful to understand relationship between pharmacokinetics (PK) and pharmacological or toxicological events in individual animals. To assess its feasibility in mice, two therapeutic antibodies were used to evaluate impacts by different blood sampling methods, sampling sites, and assay platforms on PK. Denosumab and Panitumumab were intravenously administered to mice and only 0.05 mL of blood sample per point was collected from jugular vein or tail vein. Blood samples were collected serially from a mouse or collected by traditional composite sampling from each mouse. Plasma concentrations of the two drugs were assayed by a generic ligand binding assay using Gyrolab or by a generic ultra-performance liquid chromatography with tandem mass spectrometry. The two assay platforms showed acceptable accuracy and precision and gave comparable PK parameters of the drugs, suggesting that both assays were successfully applied to the PK assessments. Comparable results in the PK profiles were noted between serial and composite blood samplings and differences in the two sampling sites did not impact PK. These findings suggest that microsampling combined with generic assays is useful to assess PK profiles of therapeutic antibodies in mice.
摘要：
从一只动物的连续血液采样对于理解个体动物中的药代动力学(PK)与药理学或毒理学事件之间的关系是有用的。为了评估其在小鼠中的可行性，两种治疗性抗体用于评估不同采血方法的影响，采样点，和PK上的测定平台。向小鼠静脉内施用Denosumab和Panitumumab,并且从颈静脉或尾静脉收集每个点仅0.05mL血液样品。从小鼠连续收集血液样品或通过传统的复合取样从每只小鼠收集。两种药物的血浆浓度通过使用Gyrolab的通用配体结合测定法或通过具有串联质谱的通用超高效液相色谱法来测定。两个测定平台显示出可接受的准确性和精密度，并给出了相当的药物PK参数，这表明两种检测方法均成功应用于PK评估。在连续和复合血液采样之间注意到PK曲线中的可比较结果,并且两个采样位点中的差异不影响PK。这些发现表明，微量采样与通用测定相结合可用于评估小鼠中治疗性抗体的PK谱。
