Estimation and simulation of kinetic-pharmacodynamic parameters of rocuronium by Bragg's dose-response-time model

Lee, Soo Il; Chung, Chan Jong; Lee, Seung Cheol; Jang, Jung Hoon

Abstract

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 300microg/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(R). The parameters, k1, k2, IR50, and gamma, were derived with either individual regression or population regression. The correlations between individual parameter and time, the simulation, and validation by infusing rocuronium 3.66microg/kg/min were examined.
RESULTS
Based on population regression, IR50 was 3.70microg/kg/min, gamma 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 168microg/kg. The effects of rocuronium 3.66microg/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.