Medical Updates in Management of Hypertonia.

Identifying the subtypes of hypertonia is becoming increasingly important. Treatment strategies, including tone-modulating surgical interventions, medication type and dosing, and chemodenervation, may differ depending on the type of hypertonia present. It is important to delineate how hypertonia interferes with function and quality of life so that the appropriate intervention can be selected at the right time. Outcomes of treatment depend heavily on clear communication of goals. Botulinum toxin should not be used in isolation but as an adjunct to rehabilitation modalities.

Population pharmacokinetics of oral baclofen in pediatric patients with cerebral palsy.

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.