A Phase I, Two-center Study of the Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Children |
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Authors: | Petroz Guy C MD; Sikich Nancy RN BScN MSc; James Michael MB ChB PhD FRCA FCA; van Dyk Hanlie MB ChB FCA
; Shafer Steven L MD; Schily Markus MB#; Lerman Jerrold MD FRCPC FANZCA |
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Institution: | Petroz, Guy C. M.D.*; Sikich, Nancy R.N., B.Sc.N., M.Sc.†; James, Michael M.B., Ch.B., Ph.D., F.R.C.A., F.C.A.(SA)‡; van Dyk, Hanlie M.B., Ch.B., F.C.A.(SA)§; Shafer, Steven L. M.D.∥; Schily, Markus M.B.#; Lerman, Jerrold M.D., F.R.C.P.C., F.A.N.Z.C.A.** |
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Abstract: | Background: To investigate dexmedetomidine in children, the authors performed an open-label study of the pharmacokinetics and pharmacodynamics of dexmedetomidine. Methods: Thirty-six children were assigned to three groups; 24 received dexmedetomidine and 12 received no drug. Three doses of dexmedetomidine, 2, 4, and 6 mu]g middle dot] kg-1 middle dot] h-1, were infused for 10 min. Cardiorespiratory responses and sedation were recorded for 24 h. Plasma concentrations of dexmedetomidine were collected for 24 h and analyzed. Pharmacokinetic variables were determined using nonlinear mixed effects modeling (NONMEM program). Cardiorespiratory responses were analyzed. Results: Thirty-six children completed the study. There was an apparent difference in the pharmacokinetics between Canadian and South African children. The derived volumes and clearances in the Canadian children were V1 = 0.81 l/kg, V2 = 1.0 l/kg, Cl1 (systemic clearance) = 0.013 l middle dot] kg-1 middle dot] min-1, Cl2 = 0.030 l middle dot] kg-1 middle dot] min-1. The intersubject variabilities for V1, V2, and Cl1 were 45%, 38%, and 22%, respectively. Plasma concentrations in South African children were 29% less than in Canadian children. The volumes and clearances in the South African children were 29% larger. The terminal half-life was 110 min (1.8 h). Median absolute prediction error for the two-compartment mammillary model was 18%. Heart rate and systolic blood pressure decreased with time and with increasing doses of dexmedetomidine. Respiratory rate and oxygen saturation (in air) were maintained. Sedation was transient. |
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