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By using a combinatory approach of in vivo neuropharmacokinetic, in vitro drug tissue binding and brain slice assays to calculate total whole brain to plasma concentration ratio ( K p,brain ), fraction of unbound alkaloids in plasma ( f u,plasma ), and volume of distribution of unbound alkaloids in the brain ( V u,brain ) respectively, the extent of unbound alkaloids in the brain ( K p,uu,brain ) yielded values of approximately 0.1, which is below the value of unity (1), thus indicating efficient efflux of the alkaloids (Yusof et al., 2019)
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