Browsing by Subject "dexmedetomidine"

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  • Bäckström, Mia (Helsingfors universitet, 2017)
    Background: Dexmedetomdine is a α2-adrenergic receptor agonist, which by binding to the α2-adrenergic receptor in the sympathetic nervous system exhibits sedative effect. Additionally, it has an analgesic and anxiolytic effect. Dexmedetomidine is registered as a sedative for use in the intensive care unit and in USA, additionally, in surgical settings. The study was conducted to characterize the pharmacokinetics in healthy volunteers through pharmacokinetic analysis methods. Methods: The clinical study was conducted on healthy 10 voluntary subjects each receiving dose of 1 µg/kg both intravenously (IV) and subcutaneously (SC). The study session lasted for 10 hours, with a wash-out period of at least 7 days between consecutive administrations. Arterial blood samples were taken to determine the plasma concentrations of dexmedetomidine. The pharmacokinetics of the IV and SC dose were determined by noncompartmental analysis (NCA) and, additionally, population modeling using nonlinear mixed effects model (NONMEM) was used to determine the pharmacokinetics of the IV dose. Results: The population's mean clearance after the IV dose was 40.0 L/h and for SC 45.6 L/h. The elimination half-life was 2 hours for IV, whereas terminal half-life was 9 hours for the SC dose. The SC bioavailability was 120 %. From the population modeling the typical elimination clearance, volume of distribution in central compartment, inter-compartmental clearance, and volume of distribution in the second compartment were 39.6 L/h, 13.7 L, 116 L/h, and 77 L, respectively. Conclussion: The obtained pharmacokinetic parameter values from NCA for IV were in line with the results from previous studies. For the SC dose the pharmacokinetic parameter values had high SD indicating high inter-individual variations. However, when the 8th subject was excluded from data analysis less SD was obtained and the result resembled more the results from other extravascular studies. The pharmacokinetic population results for IV dexmedetomidine were similar to previous studies on healthy subjects. Weight was used as a covariate, and was modeled by allometrically scaling the parameters. From the results it is shown that the covariate improved the model's goodness of fit.
  • Hector, Rachel C.; Rezende, Marlis L.; Mama, Khursheed R.; Steffey, Eugene P.; Raekallio, Marja R.; Vainio, Outi M. (2021)
    Objective To evaluate the effects of combined infusions of vatinoxan and dexmedetomidine on inhalant anesthetic requirement and cardiopulmonary function in dogs. Study design Prospective experimental study. Methods A total of six Beagle dogs were anesthetized to determine sevoflurane minimum alveolar concentration (MAC) prior to and after an intravenous (IV) dose (loading, then continuous infusion) of dexmedetomidine (4.5 mu g kg(-1) hour(-1)) and after two IV doses of vatinoxan in sequence (90 and 180 mu g kg(-1) hour(-1)). Blood was collected for plasma dexmedetomidine and vatinoxan concentrations. During a separate anesthesia, cardiac output (CO) was measured under equivalent MAC conditions of sevoflurane and dexmedetomidine, and then with each added dose of vatinoxan. For each treatment, cardiovascular variables were measured with spontaneous and controlled ventilation. Repeated measures analyses were performed for each response variable; for all analyses, p <0.05 was considered significant. Results Dexmedetomidine reduced sevoflurane MAC by 67% (0.64 +/- 0.1%), mean +/- standard deviation in dogs. The addition of vatinoxan attenuated this to 57% (0.81 +/- 0.1%) and 43% (1.1 +/- 0.1%) with low and high doses, respectively, and caused a reduction in plasma dexmedetomidine concentrations. Heart rate and CO decreased while systemic vascular resistance increased with dexmedetomidine regardless of ventilation mode. The co-administration of vatinoxan dose-dependently modified these effects such that cardiovascular variables approached baseline. Conclusions and clinical relevance IV infusions of 90 and 180 mu g kg(-1) hour(-1) of vatinoxan combined with 4.5 mu g kg(-1) hour(-1) dexmedetomidine provide a meaningful reduction in sevoflurane requirement in dogs. Although sevoflurane MAC-sparing properties of dexmedetomidine in dogs are attenuated by vatinoxan, the cardiovascular function is improved. Doses of vatinoxan >180 mu g kg(-1) hour(-1) might improve cardiovascular function further in combination with this dose of dexmedetomidine, but beneficial effects on anesthesia plane and recovery quality may be lost.