title: A comparison between dosages and plasma concentrations of dexmedetomidine in clinically ill patients: a prospective, observational, cohort study in Japan.
abstract: BACKGROUND
  Dexmedetomidine is a highly selective central α2-agonist with anesthetic and analgesic properties for patients in intensive care units. There is little information about the relationship between dosage and plasma concentration during long drug infusions of dexmedetomidine in critically ill patients, especially in Asians. In addition, the administration of dexmedetomidine with a dosage of 0.2-0.7 μg/kg/h in Japan is different from that with a dosage of 0.2-1.4 μg/kg/h in European countries and the USA. There has been concern about obtaining an effective concentration with a small dosage and estimating the relationship between dosage and plasma concentration. We conducted a prospective, observational, cohort study measuring plasma dexmedetomidine concentrations.
  
  
  METHODS
  Plasma dexmedetomidine concentrations of 67 samples from 34 patients in an intensive care unit for 2 months were measured by ultra performance liquid chromatography coupled with tandem mass spectrometry using single-blind method, and the correlation coefficient between dosages and plasma concentrations was estimated. Exclusion criteria included young patients (<16 years) and samples obtained from patients in which the dosage of dexmedetomidine was changed within 3 h.
  
  
  RESULTS
  Among the patients, 20 (58.8%) of the 34 received dexmedetomidine at 0.20-0.83 μg/kg/h, and in 40 of the 67 samples for which dexmedetomidine had been administered, this occurred for a median duration of 18.5 h (range, 3-87 h). The range of the dexmedetomidine plasma concentration was 0.22-2.50 ng/ml. By comparison with other studies, with a dosage of 0.2-0.7 μg/kg/h, the patients in this setting could obtain an effective dexmedetomidine concentration. The plasma dexmedetomidine concentration was moderately correlated with the administered dosage (r = 0.653, P < 0.01). The approximate linear equation was y = 0.171x + 0.254. The range of Richmond Agitation-Sedation Scale was 0 to -5.
  
  
  CONCLUSIONS
  We concluded that, with a dosage of 0.2-0.83 μg/kg/h, the patients in this setting could obtain an effective dexmedetomidine concentration of 0.22-2.50 ng/ml. In addition, the plasma dexmedetomidine concentration was moderately correlated with the administered dosage (r = 0.653, P < 0.01).
  
  
  BACKGROUND
  University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) UMIN000009115.
authors.affiliation: Department of Anesthesiology and Medical Crisis Management, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601 Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Laboratory of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526 Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Laboratory of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526 Japan.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Anesthesiology and Medical Crisis Management, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601 Japan.
authors.forename: Saya
authors.initials: S
authors.lastname: Yoshizawa
authors.affiliation: Department of Anesthesiology and Medical Crisis Management, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601 Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Tomita
authors.affiliation: Department of Anesthesiology and Medical Crisis Management, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601 Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maeda
authors.affiliation: Department of Anesthesiology and Medical Crisis Management, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601 Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Taka
authors.affiliation: Department of Anesthesiology and Medical Crisis Management, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601 Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Muramatsu
authors.affiliation: Department of Anesthesiology and Medical Crisis Management, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601 Japan.
authors.forename: Youichiro
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Department of Anesthesiology and Medical Crisis Management, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601 Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hirate
authors.affiliation: Laboratory of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526 Japan.
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Toyo'oka
authors.affiliation: Department of Anesthesiology and Medical Crisis Management, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601 Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sobue
keywords: Dexmedetomidine; Plasma concentration; Ultra performance liquid chromatography tandem mass spectrometry