• María-Gabriela Pérez-Guillé, Alejandra Toledo-López, Liliana Rivera-Espinosa, Radames Alemon-Medina, Chiharu Murata, Ismael Lares-Asseff, Juan Luis Chávez-Pacheco, Josefina Gómez-Garduño, Ana-Lilia Zamora Gutiérrez, Claudia Orozco-Galicia, Karina Ramírez-Morales, and Gustavo Lugo-Goytia.
• From the Departamento de Farmacología, Instituto Nacional de Pediatría, México.
• Anesth. Analg. 2018 Sep 1; 127 (3): 716-723.

BackgroundDexmedetomidine (DEX) is an α-2 adrenergic agonist with sedative and analgesic properties. Although not approved for pediatric use by the Food and Drug Administration, DEX is increasingly used in pediatric anesthesia and critical care. However, very limited information is available regarding the pharmacokinetics of DEX in children. The aim of this study was to investigate DEX pharmacokinetics and pharmacodynamics (PK-PD) in Mexican children 2-18 years of age who were undergoing outpatient surgical procedures.MethodsThirty children 2-18 years of age with American Society of Anesthesiologists physical status score of I/II were enrolled in this study. DEX (0.7 μg/kg) was administered as a single-dose intravenous infusion. Venous blood samples were collected, and plasma DEX concentrations were analyzed with a combination of high-performance liquid chromatography and electrospray ionization-tandem mass spectrometry. Population PK-PD models were constructed using the Monolix program.ResultsA 2-compartment model adequately described the concentration-time relationship. The parameters were standardized for a body weight of 70 kg by using an allometric model. Population parameters estimates were as follows: mean (between-subject variability): clearance (Cl) (L/h × 70 kg) = 20.8 (27%); central volume of distribution (V1) (L × 70 kg) = 21.9 (20%); peripheral volume of distribution (V2) (L × 70 kg) = 81.2 (21%); and intercompartmental clearance (Q) (L/h × 70 kg) = 75.8 (25%). The PK-PD model predicted a maximum mean arterial blood pressure reduction of 45% with an IC50 of 0.501 ng/ml, and a maximum heart rate reduction of 28.9% with an IC50 of 0.552 ng/ml.ConclusionsOur results suggest that in Mexican children 2-18 years of age with American Society of Anesthesiologists score of I/II, the DEX dose should be adjusted in accordance with lower DEX clearance.

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