Abstract
A universal pharmacokinetic model was developed from pooled paediatric and adult data (40.6 postmenstrual weeks, 70.8 years, 3.1–152 kg). A three-compartment pharmacokinetic model with first-order elimination was superior to a two-compartment model to describe these pooled dexmedetomidine data. Population parameter estimates (population parameter variability%) were clearance (CL) 0.9 L/min/70 kg (36); intercompartmental clearances (Q2) 1.68 L/min/70 kg (63); Q3 0.62 L/min/70 kg (90); volume of distribution in the central compartment (V1) 25.2 L/70 kg (103.9); rapidly equilibrating peripheral compartment (V2) 34.4 L/70 kg (41.8); slow equilibrating peripheral compartment (V3) 65.4 L/70 kg (62). Obesity was best described by fat-free mass for clearances and normal fat mass for volumes with a factor for fat mass (FfatV) of 0.293. Models describing dexmedetomidine pharmacokinetics in adults can be applied to children by accounting for size (allometry) and age (maturation). This universal dexmedetomidine model is applicable to a broad range of ages and weights: neonates through to obese adults. Lean body weight is a better size descriptor for dexmedetomidine clearance than total body weight. This parameter set could be programmed into target-controlled infusion pumps for use in a broad population.
Highlights
Total intravenous anaesthesia (TIVA) has been widely practiced in adult anaesthesia since the introduction of propofol into routine clinical practice in 1982
Adult parameter sets are published for propofol [2,3], remifentanil [4], sufentanil [5], alfentanil [6], dexmedetomidine [7], and ketamine [8]
We have derived a universal population PK model for dexmedetomidine that is applicable to both children and adults with a wide range of weights
Summary
Total intravenous anaesthesia (TIVA) has been widely practiced in adult anaesthesia since the introduction of propofol into routine clinical practice in 1982. Parameter sets for children have been published for propofol [9,10], remifentanil [11], and dexmedetomidine [12]. Propofol currently remains the only drug available for children in many TCI pumps. Due to this scarcity of paediatric PK models in commercially available TCI pumps, adult PK parameters (e.g., those described by Minto et al for remifentanil [4]) continue to be used in TCI pumps for children, despite both V and CL (expressed as mL/min/kg) decreasing with increasing age [11,13]
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