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Nonclinical and clinical data were analyzed using noncompartmental analysis and nonlinear mixed-effect modeling approaches. Both allometric methods produced CSF exposure predictions within twofold of the observed exposure parameters maximum plasma concentration (Cmax ) and area under the curve (AUC). Furthermore, cross-species qualification produced consistent and reasonable PK profile predictions, which supported the allometric scaling of model parameters. The challenges faced in orphan drug development place an increased importance on