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The Kp,uu,brain values of those compounds increased up to 2.86-fold from 4 to 24 hours. The CL calculated from infusion rate over steady-state concentration from the 24-hour infusion studies was more consistent with the CL from the intravenous bolus studies than that from 4-hour infusion studies (CL avg. fold of difference 1.19-1.44 vs. 2.1. The compartmental analysis using one- and two-compartment models demonstrated better performance than NCA regardless of study design. In addition, volume of distribution at steady state and t1/2,

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