Stereoselective block of hERG channel by (S)-methadone and QT interval prolongation in CYP2B6 slow metabolizers.

Methadone inhibits the cardiac potassium channel hERG and can cause a prolonged QT interval. Methadone is chiral but its therapeutic activity is mainly due to (R)-methadone. Whole-cell patch-clamp experiments using cells expressing hERG showed that (S)-methadone blocked the hERG current 3.5-fold more potently than (R)-methadone (IC50s (half-maximal inhibitory concentrations) at 37 degrees C: 2 and 7 microM). As CYP2B6 slow metabolizer (SM) status results in a reduced ability to metabolize (S)-methadone, electrocardiograms, CYP2B6 genotypes, and (R)- and (S)-methadone plasma concentrations were obtained for 179 patients receiving (R,S)-methadone. The mean heart-rate-corrected QT (QTc) was higher in CYP2B6 SMs (*6/*6 genotype; 439+/-25 ms; n=11) than in extensive metabolizers (non *6/*6; 421+/-25 ms; n=168; P=0.017). CYP2B6 SM status was associated with an increased risk of prolonged QTc (odds ratio=4.5, 95% confidence interval=1.2-17.7; P=0.03). This study reports the first genetic factor implicated in methadone metabolism that may increase the risk of cardiac arrhythmias and sudden death. This risk could be reduced by the administration of (R)-methadone.

Impact of videogame playing on glucose metabolism in children with type 1 diabetes.

Phan-Hug F, Thurneysen E, Theintz G, Ruffieux C, Grouzmann E. Impact of videogame playing on glucose metabolism in children with type 1 diabetes. Time spent playing videogames (VG) occupies a continually increasing part of children's leisure time. They can generate an important state of excitation, representing a form of mental and physical stress. This pilot study aimed to assess whether VG influences glycemic balance in children with type 1 diabetes. Twelve children with type 1 diabetes were subjected to two distinct tests at a few weeks interval: (i) a 60-min VG session followed by a 60-min rest period and (ii) a 60-min reading session followed by a 60-min rest period. Heart rate, blood pressure, glycemia, epinephrine (E), norepinephrine (NE), cortisol (F), and growth hormone (GH) were measured at 30 min intervals from -60 to +120 min. Non-parametric Wilcoxon tests for paired data were performed on Δ-values computed from baseline (0 min). Rise in heart rate (p = 0.05) and NE increase (p = 0.03) were shown to be significantly higher during the VG session when compared to the reading session and a significant difference of Δ-glycemic values was measured between the respective rest periods. This pilot study suggests that VG playing could induce a state of excitation sufficient to activate the sympathetic system and alter the course of glycemia. Dietary and insulin dose recommendations may be needed to better control glycemic excursion in children playing VG.