A population analysis of Intravenous Dexmedetomidine in Korean
SeungHwan Lee, MD, Bo-Hyung Kim, MD, Donghoon Shin, MD, Min Kyu Park, MD, Sang-Goo Shin, MD, PhD, Kyung-Sang Yu, MD, PhD, In-Jin Jang, MD, PhD
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea
Objectives: Dexmedetomidine is a selective alpha2-adrenoreceptor agonist used for sedation in critically ill patients. The aim of this study was develop a population pharmacokinetic model of intravenous dexmedetomidine in Korean and compare previously reported pharmacokinetic data.
Methods: Dexmedetomidine concentration-time data were obtained from a randomized, double-blind, placebo-controlled, phase 1 study in three parallel dosage groups. Three intravenous dexmedetomidine dosing regimen was used; 3 µg/kg/h for 10 minutes followed by 0.17 µg/kg/h for 50 minutes, 6 µg/kg/h for 10 minutes followed by 0.34 µg/kg/h for 50 minutes and 3.7 µg/kg/h for 35 minutes followed by 0.7 µg/kg/h for 25 minutes. Plasma samples for pharmacokinetic analysis were taken at pre-dose and 0.17 h, 0.58 h, 0.75 h, 1 h, 1.17 h, 1.33 h, 1.5 h, 2 h, 3 h, 4 h, 7 h, 10 h, 12 h postdose. Population pharmacokinetic model was developed using NONMEM®, version VI) and PsN.
Results: : A total of 208 concentrations form 16 subjects were included in population analysis. Mean (±SD) age was 26.4 ± 2.7 years and weight was 71.2 ± 8.0 kg. Pharmacokinetic of dexmedetomidine was best described using a two-compartment model with first-order kinetics. Population mean estimate (SE) of clearance (CL) was 33.0 (0.756) L/h, central volume of distribution (V1) was 19.7 (0.565) L, inter-compartment clearance (Q) was 65.8 (3.41) L/h and peripheral volume of distribution (V2) was 61.4 (2.47) L. Most of the data were within 5th and 95th percentile in visual predictive check, which indicated that the model describes the pharmacokinetics of dexmedetomidine adequately.
Conclusions: A two-compartment model with first-order elimination adequately characterized the pharmacokinetics of dexmedetomidine. Application of population pharmacokinetic model will be helpful for dose selection in clinical use.