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Dexmedetomidine pharmacodynamics in healthy volunteers, 2 : haemodynamic profile

(2017) BRITISH JOURNAL OF ANAESTHESIA. 119(2). p.211-220
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Abstract
Background. Dexmedetomidine, a selective alpha(2)-adrenoreceptor agonist, has unique characteristics, with little respiratory depression and rousability during sedations. We characterized the haemodynamic properties of dexmedetomidine by developing a pharmacokinetic-pharmacodynamic (PKPD) model with a focus on changes in mean arterial blood pressure (MAP) and heart rate. Methods. Dexmedetomidine was delivered i.v. to 18 healthy volunteers in a step-up fashion by target-controlled infusion using the Dyck model. Exploratory PKPD modelling and covariate analysis were conducted in NONMEM. Results. Our model adequately describes dexmedetomidine-induced hypotension, hypertension, and bradycardia, with a greater effective concentration for the hypertensive effect. Changes in MAP were best described by a double-sigmoidal Emax model with hysteresis. Covariate analysis revealed no significant covariates apart from age on the baseline MAP in the population pharmacokinetic model used to develop this PKPD model. Simulations revealed good general agreement with published descriptive studies of haemodynamics after dexmedetomedine infusion. Conclusions. The present integrated PKPD model should allow tighter control over the desired level of sedation, while limiting potential haemodynamic side-effects.
Keywords
ADULT HUMAN VOLUNTEERS, INTRAVENOUS DEXMEDETOMIDINE, PLASMA-CONCENTRATIONS, CONTROLLED INFUSION, HUMANS, HYDROCHLORIDE, MODEL, dexmedetomidine, haemodynamics, healthy volunteers, hypnotics and, sedatives, pharmacology

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Chicago
Colin, Pieter, LN Hannivoort, DJ Eleveld, KMEM Reyntjens, AR Absalom, HEM Vereecke, and Michel Struys. 2017. “Dexmedetomidine Pharmacodynamics in Healthy Volunteers, 2 : Haemodynamic Profile.” British Journal of Anaesthesia 119 (2): 211–220.
APA
Colin, P., Hannivoort, L., Eleveld, D., Reyntjens, K., Absalom, A., Vereecke, H., & Struys, M. (2017). Dexmedetomidine pharmacodynamics in healthy volunteers, 2 : haemodynamic profile. BRITISH JOURNAL OF ANAESTHESIA, 119(2), 211–220.
Vancouver
1.
Colin P, Hannivoort L, Eleveld D, Reyntjens K, Absalom A, Vereecke H, et al. Dexmedetomidine pharmacodynamics in healthy volunteers, 2 : haemodynamic profile. BRITISH JOURNAL OF ANAESTHESIA. 2017;119(2):211–20.
MLA
Colin, Pieter et al. “Dexmedetomidine Pharmacodynamics in Healthy Volunteers, 2 : Haemodynamic Profile.” BRITISH JOURNAL OF ANAESTHESIA 119.2 (2017): 211–220. Print.
@article{8532514,
  abstract     = {Background. Dexmedetomidine, a selective alpha(2)-adrenoreceptor agonist, has unique characteristics, with little respiratory depression and rousability during sedations. We characterized the haemodynamic properties of dexmedetomidine by developing a pharmacokinetic-pharmacodynamic (PKPD) model with a focus on changes in mean arterial blood pressure (MAP) and heart rate. 
Methods. Dexmedetomidine was delivered i.v. to 18 healthy volunteers in a step-up fashion by target-controlled infusion using the Dyck model. Exploratory PKPD modelling and covariate analysis were conducted in NONMEM. 
Results. Our model adequately describes dexmedetomidine-induced hypotension, hypertension, and bradycardia, with a greater effective concentration for the hypertensive effect. Changes in MAP were best described by a double-sigmoidal Emax model with hysteresis. Covariate analysis revealed no significant covariates apart from age on the baseline MAP in the population pharmacokinetic model used to develop this PKPD model. Simulations revealed good general agreement with published descriptive studies of haemodynamics after dexmedetomedine infusion. 
Conclusions. The present integrated PKPD model should allow tighter control over the desired level of sedation, while limiting potential haemodynamic side-effects.},
  author       = {Colin, Pieter and Hannivoort, LN and Eleveld, DJ and Reyntjens, KMEM and Absalom, AR and Vereecke, HEM and Struys, Michel},
  issn         = {0007-0912},
  journal      = {BRITISH JOURNAL OF ANAESTHESIA},
  keywords     = {ADULT HUMAN VOLUNTEERS,INTRAVENOUS DEXMEDETOMIDINE,PLASMA-CONCENTRATIONS,CONTROLLED INFUSION,HUMANS,HYDROCHLORIDE,MODEL,dexmedetomidine,haemodynamics,healthy volunteers,hypnotics and,sedatives,pharmacology},
  language     = {eng},
  number       = {2},
  pages        = {211--220},
  title        = {Dexmedetomidine pharmacodynamics in healthy volunteers, 2 : haemodynamic profile},
  url          = {http://dx.doi.org/10.1093/bja/aex086},
  volume       = {119},
  year         = {2017},
}

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