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

Summary What is known and ObjectiveThe 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. MethodFifteen 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 0.6 μg/kg dexmedetomidine for 10 minutes 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. Results and discussionThe 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 foll...
Source: Journal of Clinical Pharmacy and Therapeutics - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research