Med (New York, N.Y.) · 2024
Closed-loop automated drug infusion regulator: A clinically translatable, closed-loop drug delivery system for personalized drug dosing.
СтатьяПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
DeRidder Louis B, Hare Kyle A, Lopes Aaron, Jenkins Josh, Fitzgerald Nina, MacPherson Emmeline, Fabian Niora, Morimoto Josh, Chu Jacqueline N, Kirtane Ameya R, Madani Wiam, Ishida Keiko, Kuosmanen Johannes L P, Zecharias Naomi, Colangelo Christopher M, Huang Hen-Wei, Chilekwa Makaya, Lal Nikhil B, Srinivasan Shriya S, Hayward Alison M, Wolpin Brian M, Trumper David, Quast Troy, Rubinson Douglas A, Langer Robert, Traverso Giovanni
Аннотация
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.
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.