作者
Louis B. DeRidder,Louis B. DeRidder,Louis B. DeRidder,Louis B. DeRidder,Kyle A. Hare,Kyle A. Hare,Aaron Lopes,Aaron Lopes,James A. Jenkins,James A. Jenkins,Nina Fitzgerald,Nina Fitzgerald,Emmeline MacPherson,Niora Fabian,Niora Fabian,Niora Fabian,Joshua Morimoto,Joshua Morimoto,Jacqueline N. Chu,Jacqueline N. Chu,Jacqueline N. Chu,Ameya R. Kirtane,Ameya R. Kirtane,Wiam Abdalla Mohammed Madani,Wiam Abdalla Mohammed Madani,Keiko Ishida,Keiko Ishida,Keiko Ishida,Johannes Kuosmanen,Johannes Kuosmanen,Naomi Zecharias,Naomi Zecharias,Naomi Zecharias,Christopher M. Colangelo,Hen-Wei Huang,Hen-Wei Huang,Hen-Wei Huang,Makaya Chilekwa,Nikhil Lal,Nikhil Lal,Nikhil Lal,Shriya S. Srinivasan,Shriya S. Srinivasan,Alison Hayward,Alison Hayward,Alison Hayward,Alison Hayward,Brian M. Wolpin,Brian M. Wolpin,Brian M. Wolpin,David L. Trumper,Troy Quast,Douglas A. Rubinson,Douglas A. Rubinson,Douglas A. Rubinson,Robert D. Langer,Robert Langer,Robert D. Langer,Robert D. Langer,Giovanni Traverso,Giovanni Traverso,Giovanni Traverso
摘要
Summary
Background
Dosing of chemotherapies is often calculated according to the weight and/or height of the patient or equations derived from these, such as body surface area (BSA). Such calculations fail to capture intra- and interindividual pharmacokinetic variation, which can lead to order of magnitude variations in systemic chemotherapy levels and thus under- or overdosing of patients. Methods
We designed and developed a closed-loop drug delivery system that can dynamically adjust its infusion rate to the patient to reach and maintain the drug's target concentration, regardless of a patient's pharmacokinetics (PK). Findings
We demonstrate that closed-loop automated drug infusion regulator (CLAUDIA) can control the concentration of 5-fluorouracil (5-FU) in rabbits according to a range of concentration-time profiles (which could be useful in chronomodulated chemotherapy) and over a range of PK conditions that mimic the PK variability observed clinically. In one set of experiments, BSA-based dosing resulted in a concentration 7 times above the target range, while CLAUDIA keeps the concentration of 5-FU in or near the targeted range. Further, we demonstrate that CLAUDIA is cost effective compared to BSA-based dosing. Conclusions
We anticipate that CLAUDIA could be rapidly translated to the clinic to enable physicians to control the plasma concentration of chemotherapy in their patients. Funding
This work was supported by MIT's Karl van Tassel (1925) Career Development Professorship and Department of Mechanical Engineering and the Bridge Project, a partnership between the Koch Institute for Integrative Cancer Research at MIT and the Dana-Farber/Harvard Cancer Center.