Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in healthy Korean subjects.
What is known and Objective: Dexmedetomidine is a selective alpha2-adrenoreceptor agonist used for sedation in critically ill patients. The current study aimed to evaluate the pharmacokinetics (PKs), pharmacodynamics and tolerability of intravenous dexmedetomidine in healthy Korean subjects. Methods...
| Publicado en: | Journal of Clinical Pharmacy & Therapeutics Vol. 37; no. 6; pp. 698 - 704 |
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| Autores principales: | , , , , , , , |
| Formato: | equations & formulas research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Wiley-Blackwell
Dec2012
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104430861&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104430861 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Dec2012 vid: 37 iid: 6 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 104430861 83005567 10.1111/j.1365-2710.2012.01357.x NLM22650799 104430861 ppf: 698 ppct: 6 formats: fmt: @attributes: type: P tig: atl: Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in healthy Korean subjects. aug: au: Lee, S. Kim, B.-H. Lim, K. Stalker, D. Wisemandle, W. Shin, S.-G. Jang, I.-J. Yu, K.-S. affil: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea sug: subj: Imidazoles Pharmacokinetics Imidazoles Pharmacodynamics Administration, Intravenous Sedation Methods Human South Korea Randomized Controlled Trials Double-Blind Studies Visual Analog Scaling Imidazoles Blood Descriptive Statistics Adolescence Adult Female Male Middle Age Young Adult Data Analysis Software Linear Regression Dose-Response Relationship, Drug Funding Source Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Female Male ab: What is known and Objective: Dexmedetomidine is a selective alpha2-adrenoreceptor agonist used for sedation in critically ill patients. The current study aimed to evaluate the pharmacokinetics (PKs), pharmacodynamics and tolerability of intravenous dexmedetomidine in healthy Korean subjects. Methods: A randomized, double-blind, placebo-controlled study with three parallel dosage groups was conducted. Twenty-four subjects were randomly assigned to placebo or one of three dexmedetomidine dosing regimens, 3 μg/kg/h for 10 min followed by 0·17 μg/kg/h for 50 min (low dose), 6 μg/kg/h for 10 min followed by 0·34 μg/kg/h for 50 min (middle dose) and 3·7 μg/kg/h for 35 min followed by 0·7 μg/kg/h for 25 min (high dose). Serial blood samples for PK analysis were taken up to 12 h. PK parameters were determined using non-compartmental methods (WinNonlin®), and a population PK model was developed using nonmem®. The sedative effect of dexmedetomidine was assessed by Ramsay sedation score and visual analogue scales/sedation. Adverse events, clinical laboratory tests, electrocardiograms, physical examinations and vital signs were monitored for tolerability assessment. Results: Six subjects were assigned to each of the three active treatment group or placebo group. The AUClast of the low-, middle- and high-dose group were 1096·8 ± 119·9 (mean ± SD) ng*h/L, 2643·0 ± 353·2 ng*h/L and 5600·6 ± 411·0 ng*h/L, respectively. PK of dexmedetomidine was best described using a two-compartment model. The typical value of the population model can be calculated using the following equations: central volume of distribution (L) = 19·9 (age/27)0·954, peripheral volume of distribution (L) = 59·4, clearance (L/h) = 33·7 (albumin level/4·3)1·42 and inter-compartment clearance (L/h) = 67·7. Sedative effects were significantly increased by dexmedetomidine compared to placebo. The blood pressure and heart rate were decreased, but oxygen saturation was maintained stable. What is new and Conclusion: Dexmedetomidine shows linear PK characteristics and dose-dependent sedative effects. A two-compartment population PK model was developed for healthy Korean subjects. The PK parameter estimates are similar in Koreans and Caucasians. pubtype: Academic Journal doctype: equations & formulas research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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