Population pharmacokinetics of rocuronium delivered by target-controlled infusion in adult patients.

BACKGROUND: Target-controlled infusion (TCI) has been recently developed and successfully implemented in clinical practice. The current study was to estimate the population pharmacokinetics of rocuronium TCI in adult patients using nonlinear mixed-effects model (NONMEM), and to investigate the influence of relevant factors in adult patients. METHODS: Fourteen ASA I-II patients undergoing elective laparoscopy operation with general anesthesia were included. After induction, all patients received rocuronium by TCI system. The beginning target plasma concentration (Cpt) was 2.0 µg/ml, then increased Cpt according to the neuromuscular transmission monitoring. The endpoint of Cpt was determined when the T₁ scale was blocked by 90% - 95%. TCI rocuronium was stopped 30 minutes before the end of the operation. Arterial blood was drawn before anesthesia at 0, 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120, 180, 240 and 360 minutes after the infusion of rocuronium was stopped for the analysis of plasma concentrations of rocuronium by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The population pharmacokinetics analysis was performed using NONMEM program. RESULTS: The pharmacokinetics of TCI rocuronium in adult patients was best described by a three-compartment model. Pharmacokinetic parameters were clearance (CL)₁ = 0.205 L/min, CL₂ = 0.324 L/min, CL₃ = 0.0292 L/min, volumes of distribution (V)₁ = 4.00 L, V₂ = 2.28 L, V₃ = 4.26 L, Vdss = 10.54 L. Both age and weight as covariates affected the pharmacokinetic parameters. V₁ and CL₁ were negatively correlated with patient age. CL₁ was positively correlated with weight. CONCLUSIONS: No pharmacokinetic change was noted when rocuronium was administered via TCI. Both age and weight as covariates affected the pharmacokinetic parameters.