Pharmacokinetics of dexmedetomidine administered to patients with end-stage renal failure and secondary hyperparathyroidism undergoing general anaesthesia.

Abstract

The primary objective of this study was to compare the pharmacokinetics of dexmedetomidine in patients with end-stage renal failure and secondary hyperparathyroidism with those in normal individuals. Fifteen patients with end-stage renal failure and secondary hyperparathyroidism (Renal-failure Group) and 8 patients with normal renal and parathyroid gland function (Control Group) received intravenous 0.6μg/kg dexmedetomidine for 10minutes before anaesthesia induction. Arterial blood samples for plasma dexmedetomidine concentration analysis were drawn at regular intervals after the infusion was stopped. The pharmacokinetics were analysed using a nonlinear mixed-effect model with NONMEM software. The statistical significance of covariates was examined using the objective function (-2 log likelihood). In the forward inclusion and backward deletion, covariates (age, weight, sex, height, lean body mass [LBM], body surface area [BSA], body mass index [BMI], plasma albumin and grouping factor [renal failure or not]) were tested for significant effects on pharmacokinetic parameters. The validity of our population model was also evaluated using bootstrap simulations. The dexmedetomidine concentration-time curves fitted best with the principles of a two-compartmental pharmacokinetic model. No covariate of systemic clearance further improved the model. The final pharmacokinetic parameter values were as follows: V1 =60.6L, V2 =222L, Cl1 =0.825L/min and Cl2 =4.48L/min. There was no influence of age, weight, sex, height, LBM, BSA, BMI, plasma albumin and grouping factor (renal failure or not) on pharmacokinetic parameters. Although the plasma albumin concentrations (35.46±4.13 vs 44.10±1.12mmol/L, respectively, P<.05) and dosage of propofol were significantly lower in the Renal-failure Group than in the Control Group (81.68±18.08 vs 63.07±13.45μg/kg/min, respectively, P<.05), there were no differences in the context-sensitive half-life and the revival time of anaesthesia between the 2 groups. The pharmacokinetics of dexmedetomidine were best described by a two-compartment model in our study. The pharmacokinetic parameters of dexmedetomidine in patients with end-stage renal failure and hyperparathyroidism were similar to those in patients with normal renal function. Further studies of dexmedetomidine pharmacokinetics are recommended to optimize its clinical use.