The pharmacokinetic profiles of biperiden (BP) in blood and in specific brain regions were investigated in rats after acute i.v. administration. The regional brain‐to‐blood unbound concentration ratios (Kpf) were also determined after 16h intravenous infusion of BP. The Kpf values ranged from 30 to 75 in the different brain regions and showed decreasing concentrations in the following order: pons + medulla oblongata, basal ganglia, amygdala, hypothalamus, thalamus, mesencephalon, bulbus olfactorius + septum, hippocampus, frontal cortex, occipital cortex, cerebellum. The relationship between BP and acetylcholine (ACh) concentrations in the brain regions was examined. ACh levels in the various brain regions ranged from 8 to 44 ng g−1 tissue. There was a significant correlation between the Kpf values of BP and the levels of ACh in the brain regions except for the pons + oblongata. BP concentrations in the brain regions after BP administration were predicted based on the physiological pharmacokinetics. There was reasonable agreement between the model predictions and the observed data.
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