Pharmacokinetics and Sedative Effects of Intranasal Dexmedetomidine in Ambulatory Pediatric Patients.

BACKGROUND: Our aim was to characterize the pharmacokinetics and sedative effects of intranasally (IN) administered dexmedetomidine used as an adjuvant in pediatric patients scheduled for magnetic resonance imaging (MRI) requiring sedation. METHODS: This was an open-label, single-period study without randomization. Pediatric patients from 5 months to 11 years of age scheduled for MRI and receiving IN dexmedetomidine for premedication as part of their care were included in this clinical trial. Single doses of 2-3 µg·kg of dexmedetomidine were applied IN approximately 1 hour before MRI. Five or 6 venous blood samples were collected over 4 hours for dexmedetomidine concentration analysis. Sedation was monitored with Comfort-B scores, and vital signs were recorded. Pharmacokinetic variables were calculated with noncompartmental methods and compared between 3 age groups (between 1 and 24 months, from 24 months to 6 years, and over 6-11 years). RESULTS: We evaluated 187 consecutive patients for suitability, of which 132 were excluded. Remaining 55 patients were recruited, of which 5 were excluded before the analysis. Data from 50 patients were analyzed. The average (standard deviation [SD]) dose-corrected peak plasma concentration (Cmax) was 0.011 liter (0.0051), and the median (interquartile range [IQR]) time to reach peak concentration (tmax) was 37 minutes (30-45 minutes). There was negative correlation with Cmax versus age (r = -0.58; 95% confidence interval [CI], -0.74 to -0.37; P < .001), but not with tmax (r = -0.14; 95% CI, 0.14-0.39; P = .35). Dose-corrected areas under the concentration-time curve were negatively correlated with age (r = -0.53; 95% CI, 0.70 to -0.29; P < .001). Median (IQR) maximal reduction in Comfort-B sedation scores was 8 (6-9), which was achieved 45 minutes (40-48 minutes) after dosing. Median (IQR) decrease in heart rate was 15% (9%-23%) from the baseline. CONCLUSIONS: Dexmedetomidine is relatively rapidly absorbed after IN administration and provides clinically meaningful but short-lasting sedation in pediatric patients.

The Importance of Direct Progeny Measurements for Correct Estimation of Effective Dose Due to Radon and Thoron.

Radon (Rn), thoron (Tn), and thoron progeny (TnP) were measured in seven inhabited areas of the uranium and thorium bearing region of Lolodorf, located in southwestern Cameroon. Then the equilibrium factor (FTn) between thoron and its progeny was determined in order to show the importance of direct progeny measurements for correct estimation of effective dose due to radon, thoron and their progenies. A total of 220 RADUET detectors were used to measure indoor radon and thoron and 130 TnP monitors for thoron progeny indoors. The arithmetic and geometric mean concentrations of Rn, Tn, and TnP were 103 and 89 Bq m-3, 173, and 118 Bq m-3, 10.7, and 7.4 Bq m-3, respectively. Total effective dose determined from radon, thoron, and their progenies was estimated at 4.2 ± 0.5 mSv y-1. Thoron equilibrium factor varied according to seasons, the type of dwelling, building materials and localities. Thoron (Tn and TnP) contribution to effective dose ranged between 3 and 80% with the average value of 53%. Total effective dose estimated from the world average equilibrium factor of 0.02 given by UNSCEAR was 2.7 ± 0.2 mSv y-1. The effective dose due to thoron varied greatly according to the different values taken by FTn and was different from that determined directly using TnP concentrations. Thus, effective dose due to thoron determined from the equilibrium factor is unreliable. Therefore, the risk of public exposure due to thoron (Tn and TnP) may therefore be higher than that of radon (Rn and RnP) in many parts of the world if FTn is no longer used in estimating total effective dose. This is not in contradiction with the UNSCEAR conclusions. It is therefore important to directly measure the radon and thoron progeny for a correct estimate of effective dose.