Current methods of drug dosing rely on physical parameters (such as sex, age and weight) that do not account for genetic and physiological differences among individual patients. These differences can greatly affect how drugs are processed in the body and can result in ineffective underdosing or toxic overdosing. Here, we describe a generalizable closed-loop system consisting of a biosensor, controller and infusion pump, and a model of drug pharmacokinetics that continuously monitors and adjusts the concentration of a given drug in the body. As proof of concept, we demonstrate that the system can maintain the concentration of doxorubicin—a widely used chemotherapy drug—in live rabbits and rats at any desired set point and in real time, while automatically compensating for large pharmacokinetic differences among individual animals and stabilizing dramatic perturbations arising from acute drug–drug interactions. The feedback-loop system opens up the possibility of tightly controlled, patient-specific dosing of chemotherapeutics and other drugs within narrow therapeutic windows.

中文翻译：

---

活体动物中循环药物水平的闭环控制

当前的药物给药方法依赖于物理参数（例如性别，年龄和体重），这些参数不能解释各个患者之间的遗传和生理差异。这些差异会极大地影响药物在体内的处理方式，并可能导致无效的剂量不足或有毒的剂量过量。在这里，我们描述了一个由生物传感器，控制器和输液泵组成的可概括性闭环系统，以及持续监测和调整体内给定药物浓度的药物药代动力学模型。作为概念验证，我们证明了该系统可以在任何期望的设定点上实时地保持活兔和大鼠中阿霉素（一种广泛使用的化疗药物）的浓度，同时自动补偿个体动物之间较大的药代动力学差异，并稳定由急性药物相互作用引起的剧烈扰动。反馈回路系统开辟了在狭窄的治疗窗口内严格控制患者特定剂量的化学治疗药物和其他药物的可能性。