PEDIATRIC PK/PD STUDY OF ORAL BACLOFEN FOR SPASTICITY ASSOCIATED WITH CP

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Baclofen is a skeletal muscle relaxant that is FDA approved for the treatment of spasticity in adults with multiple sclerosis and spinal cord injury. Baclofen, the p-chlorophenyl derivative of Gamma Amino Butyric acid (GABA), binds to GABA receptors, primarily in the spinal cord, where it reduces excitatory neurotransmitter release. Baclofen has both pre and post synaptic effects on monosynaptic and polysynaptic pathways (Gracies, 1997). The desired clinical effects are an attenuation of short and long latency stretch responses, and a relaxation of muscle spasms. Baclofen has been shown to reduce spasticity, painful muscle spasms and clonus in adults although data are limited and somewhat inconsistent (Chou et al 2004, Dario & Tomei 2004). Some reports suggest that baclofen may be more effective in patients with spasticity of spinal origin rather than cerebral origin (Knutsson et al 1974). Although oral baclofen has been used for several decades for the treatment of spasticity in adults and in children, there is very little data regarding the pharmacokinetic (PK) or pharmacodynamic (PD) properties of baclofen in children. Therefore, pediatric guidelines, including dose ranges, dosing schedules, dose escalation strategies and anticipated side effects are extrapolated from adult data and require an assumption that safety and efficacy in children is comparable to that in adults. Furthermore, there is wide variability in dosing strategies among practitioners who treat children with cerebral palsy (CP) with respect to starting doses, maximum doses and rates of dose escalation.