title: Brain regional pharmacokinetics of biperiden in rats.
abstract: 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 16 h 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.
authors.affiliation: Hospital Pharmacy, Kanazawa University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yokogawa
authors.forename: E
authors.initials: E
authors.lastname: Nakashima
authors.forename: J
authors.initials: J
authors.lastname: Ishizaki
authors.forename: M
authors.initials: M
authors.lastname: Hasegawa
authors.forename: H
authors.initials: H
authors.lastname: Kido
authors.forename: F
authors.initials: F
authors.lastname: Ichimura
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001712:Biperiden / Q000097:blood / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
chemical_list: D001712:Biperiden; D002794:Choline; D000109:Acetylcholine