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Tramadol is a &mu, opioid receptor agonist and a monoamine reuptake inhibitor. O-desmethyltramadol (M1), the major active metabolite of tramadol, is produced by CYP2D6. A physiologically-based pharmacokinetic model was developed to predict changes in time-concentration profiles for tramadol and M1 according to dosage and CYP2D6 genotypes in the Korean population. Parallel artificial membrane permeation assay was performed to determine tramadol permeability, and the metabolic clearance of M1 was determined using human liver microsomes. Clinical study data were used to develop the model. Other physicochemical and pharmacokinetic parameters were obtained from the literature. Simulations for plasma concentrations of tramadol and M1 (after 100 mg tramadol was administered five times at 12-h intervals) were based on a total of 1000 virtual healthy Koreans using SimCYP&reg, simulator. Geometric mean ratios (90% confidence intervals) (predicted/observed) for maximum plasma concentration at steady-state (Cmax,ss) and area under the curve at steady-state (AUClast,ss) were 0.79 (0.69&ndash, 0.91) and 1.04 (0.85&ndash, 1.28) for tramadol, and 0.63 (0.51&ndash, 0.79) and 0.67 (0.54&ndash, 0.84) for M1, respectively. The predicted time&ndash, concentration profiles of tramadol fitted well to observed profiles and those of M1 showed under-prediction. The developed model could be applied to predict concentration-dependent toxicities according to CYP2D6 genotypes and also, CYP2D6-related drug interactions.

For many students, school-organized sports play an important role in students' academic and social experiences. This study focuses on the effects of participation in school-organized sports on academic achievement and students' perceptions of family support, teacher and community support, and school safety. Data were obtained from the 2010 administration of the Minnesota Student Survey, resulting in a total sample of 29,535 12th grade students of which 12,849 participated regularly (at least 1–2 times per week) in school-organized sports. Propensity score matching was used to match similar students who voluntarily participated in school sports with those who were not involved in any school sports. Participation in school sports was associated with higher GPAs, favorable perceptions of school safety, and increased perceptions of family and teacher/community support. Guidance for parents, educators, and policymakers on how to further promote students' academic and social success are discussed.