Bragg의 용량-반응-시간모형으로 rocuronium의 동학-약역학모수의 추정과 모의실험 (Estimation and simulation of kinetic-pharmacodynamic parameters of rocuronium by Bragg’s dose-response-time model)

서지정보

· 발행기관 : 대한마취통증의학회
· 수록지 정보 : Anesthesia and Pain Medicine / 6권 / 1호 / 67 ~ 74페이지
· 저자명 : 이수일, 정찬종, 이승철, 장정훈

초록

Background:The effect-time data involves some pharmacokinetic (PK) information. Bragg model could derive the information from pharmacodynamic (PD) data alone. After administering rocuronium, we collected tension data without these plasma concentration values. We determined kinetic-pharmacodynamic (K-PD) parameters, simulated the predictions of effect-time relation at different amount of dose, and validated the calculated infusion rates (IR) by comparing with IR directly measured.
Methods: Thirteen dexterous male patients were given rocuronium 300μg/kg during propofol-fentanyl anesthesia. Twitch tensions of the right adductor pollicis in response to supramaximal single twitch stimulation every 10 seconds were measured until muscle paralysis recovered by 70 ± 10% of control. The above data were fitted to Bragg equation, using Tablecurve3DⓇ. The parameters, k1, k2, IR50, and γ, were derived with either individual regression or population regression. The correlations between individual parameter and time, the simulation, and validation by infusing rocuronium 3.66μg/kg/min were examined.
Results: Based on population regression, IR50 was 3.70μg/kg/min, γ was 4.51, k1 (keo) was 0.71/min, and k2 (k10) was 0.022/min. The longer the duration of rocuronium action was, the smaller the values of IR50 and k2 were (correlation coefficient: −0.92, −0.61, respectively). ED50 calculated (= IR50/k2) was 168μg/kg. The effects of rocuronium 3.66μg/kg/min were estimated (45% by direct measurement, 49% by population parameters, and 21% by individual parameters).
Conclusions: The results of infusion rate validation suggests that population parameters may better be applicable than individual post hoc parameters to predicting the clinically relevant effect-time relations.(Anesth Pain Med 2011; 6: 67∼74)

영어초록

Background:The effect-time data involves some pharmacokinetic (PK) information. Bragg model could derive the information from pharmacodynamic (PD) data alone. After administering rocuronium, we collected tension data without these plasma concentration values. We determined kinetic-pharmacodynamic (K-PD) parameters, simulated the predictions of effect-time relation at different amount of dose, and validated the calculated infusion rates (IR) by comparing with IR directly measured.
Methods: Thirteen dexterous male patients were given rocuronium 300μg/kg during propofol-fentanyl anesthesia. Twitch tensions of the right adductor pollicis in response to supramaximal single twitch stimulation every 10 seconds were measured until muscle paralysis recovered by 70 ± 10% of control. The above data were fitted to Bragg equation, using Tablecurve3DⓇ. The parameters, k1, k2, IR50, and γ, were derived with either individual regression or population regression. The correlations between individual parameter and time, the simulation, and validation by infusing rocuronium 3.66μg/kg/min were examined.
Results: Based on population regression, IR50 was 3.70μg/kg/min, γ was 4.51, k1 (keo) was 0.71/min, and k2 (k10) was 0.022/min. The longer the duration of rocuronium action was, the smaller the values of IR50 and k2 were (correlation coefficient: −0.92, −0.61, respectively). ED50 calculated (= IR50/k2) was 168μg/kg. The effects of rocuronium 3.66μg/kg/min were estimated (45% by direct measurement, 49% by population parameters, and 21% by individual parameters).
Conclusions: The results of infusion rate validation suggests that population parameters may better be applicable than individual post hoc parameters to predicting the clinically relevant effect-time relations.(Anesth Pain Med 2011; 6: 67∼74)

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