BM1022 Lecture Notes - Lecture 26: Lipophilicity, Enzyme, Cytochrome P450

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16 Jul 2018
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Most reactions are equilibrium reactions so if some product is removed (ie by absorpt. Molecules need to be un-ionized (lipophilic) to cross membranes. Main aim is to convert from lipophilic (good for absorption) to hydrophilic, readily solu and therefore excreted with urine (ie removal of toxins). Enzymes in gut wall, blood, lungs and liver. Main superfamily of enzymes cyp450 (cytochrome p450) (liver). Bioavailability: absorption and proportion of drug that remains after first pass of liver. Hepatic extraction ratio: proportion of drug removed by liver cells via metabolism. Plasma binding (enzymes are inside cells, only free drug can pass into cells). Drug pka (hydrophilic will enter liver cells) (blood ph 7. 4). soluble in water ver. Clearance is volume of blood cleared irreversibly of drug per unit time. Calculated from blood flow to liver and hepatic extraction. Cl(h) = e(h) x q(h) units = l/h or ml/min. 40% total blood flow goes through portal circulation.

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