PubMed · 1987 · 35 citations · 0 references
PharmacyPharmacokineticsPharmacologyNeurochemistryPharmacokinetic ModelingToxicokineticsBlood-brain Barrier PenetrationBlood-brain Barrier ToxicityConcentration-effect RelationshipsDrug DispositionDrug Distribution KineticsProtein BindingBilirubin BindingBilirubin KineticsBilirubin UptakeBlood - Brain Barrier UptakeBrain ExposureCapillary Transit TimeDissociation Rate ConstantsRate Constants
A mathematical model is presented to describe quantitatively the uptake of bilirubin into the brain from blood, under conditions of extensive binding to plasma proteins. The model relates bilirubin uptake to the rate constants for dissociation and association of the albumin/bilirubin complex and to the transit time of blood through brain capillaries. A rational basis is given for deciding between the total or the free bilirubin concentration as an appropriate indicator of brain exposure to the toxic effects of bilirubin. The effect of competition for binding sites by drugs such as sulfonamides on the brain uptake of bilirubin is also described quantitatively.