PHIL 2130 Chapter Notes - Chapter 2.3: Partition Coefficient, P-Glycoprotein, Multiple Drug Resistance
6 May 2020
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Pk deficits could be due to poor solubility, absorption, high first pass, high clearance, low bioavailability, quick half life, non linear kinetics, inhibition, reactive metabolites, polymorphic metabolism. Size is important for capillaries, negative charge has less absorption. Heptaocytes, renal tubules and bbb are high dependent on these factors. logp = log([drugoct]/[drugwater]). Higher log p means more liphophilic, better absorption. Amino acids polar won"t absorb well, ether is less polar so better. Transporters in bbb may cause efflux i. e. vinblastine, vincristine. P glycoprotein is a gene product of multidrug resistance protein mdr1. Large km = dissociates, less binding, small km = tight binding, good for reaction. Competitive inhibition: km increases meaning lower affinity, vmax unchanged. If ki << km then it"s effective as an inhibitor since lower ki means a tighter binding. Gut: large sa, glycocalyx sugar chains hydrated with water forming unstirred water layer hard for lipids to get through, gastric emptyping, tranporters, bacteria, blood flow.
