PHIL 2130 Lecture Notes - Lecture 1: Slco1B1, Ace Inhibitor, Benzoic Acid
6 May 2020
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Rapidly perfused: adrenals, kidneys, liver, heart, brain. Low tissue binding = lower volume, high tissue binding = higher volume (seems more occupied) Tissue binding >> plasma binding is better for distribution, don"t want binding in blood. Liver: makes molecules polar, excretion of bile, enterohepatic recirculation. Liver canalicular transporters (efflux into bile: pgp, bcrp, mrp2, bsep: bile salt export pump, bile acids, statins, mate (multidrug and toxic compound extrusion, cationic dyes, aciflavine, ethidium aminoglycosides, fluoroqunolones, ciprofloxacin, doxorubicin. Biliary secretion: enterohepatic circulation (ehc) of bile acids, micelles, excretion of bile adds, drug excretion and ehc leads to increased duration of drugs. Liver toxicity: bile acid or bilirubin accumulation. Deficiencies in hepatobiliary transport: mrp2 deficiency = dubin johnson syndrome, bsep deficiency = progressive familial intrahepatic cholestatis type 1 (pfic1). Mutation in bsep = type 2 (pfic 2) Inulin best gfr marker, not absorbed or secreted.
