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Objective To characterize the population pharmacokinetics (PK) of oral baclofen and assess impact of patient-specific covariates in children with cerebral palsy (CP) in order to support its clinical use. Subjects design Children (2-17 years of age) with CP received a dose of titrated oral baclofen from 2.5 mg 3 times a day to a maximum tolerated dose of up to 20 mg 4 times a day. PK sampling followed titration of 10-12 weeks. Serial R- and S-baclofen plasma concentrations were measured for up to 16 hours in 49 subjects. Population PK modeling was performed using NONMEM 7.1 (ICON PLC; Ellicott City, Maryland). Results R- and S-baclofen showed identical concentration-time profiles. Both baclofen enantiomers exhibited linear and dose/kg-proportional PK, and no sex differences were observed. Average baclofen terminal half-life was 4.5 hours. A 2-compartment PK model with linear elimination and transit absorption steps adequately described concentration-time profiles of both baclofen enantiomers. The mean population estimate of apparent clearance/F was 0.273 L/h/kg with 33.4% inter-individual variability (IIV), and the apparent volume of distribution (Vss/F) was 1.16 L/kg with 43.9% IIV. Delayed absorption was expressed by a mean transit time of 0.389 hours with 83.7% IIV. Body weight, a possible genetic factor, and age were determinants of apparent clearance in these children. Conclusion The PK of oral baclofen exhibited dose-proportionality and were adequately described by a 2-compartment model. Our population PK findings suggest that baclofen dosage can be based on body weight (2 mg/kg per day) and the current baclofen dose escalation strategy is appropriate in the treatment of children with CP older than 2 years of age.

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This experiential learning strategy engages students to increase awareness of professional core competencies recommended by various professional organizations. Aimed across the accounting curriculum, this activity allows individuals to explore competencies recommended to bridge the professional skills gap and develop a plan to acquire these necessary skills. The strategy activities include (1) initial class discussion of perceptions; (2) personality test for a personal SWOT analysis, (3) research of a professional competency framework; (4) personal assessment of competencies, including demonstrative examples, analysis of personal skill development experiences and self-rating of skills; (5) reflective group discussion to identify gaps in the individual student's skills assessment; (6) individual competency development plan for underrated skills and (7) summary discussion for strategies for how to acquire/improve skills towards career success. This experiential learning opportunity benefits students by increasing awareness of necessary professional competencies and creating a skills development plan. The result of this strategy is that students are introduced to a process they can use throughout their academic and professional careers to facilitate the acquisition of necessary skills for success as an accounting professional. This project has been piloted for over 12 years at seven universities with students ranging from freshman to graduate levels across five core areas of accounting and can be scaled to any class size.