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Unformatted text preview: Compartmental Models One Two Compartments 1 Problem of the Day • A 70 y.o. is to be treated with digoxin tablets. What should the daily dose (in mg) be to achieve and maintain a target plasma level of 1 ng/ml? How long will it take to achieve 90% of plateau values? You can assume: Cl R =41.5 mL/min (for digoxin) in this 43 kg patient, f e =0.68;Vss=6.7 L/kg; F=0.75. Two Compartments V i V t k e Drug given into “initial” volume (V i, central compartment) and it slowly distributes into larger “tissue” volume (V t, peripheral compartment) Drug Eliminated from the central compartment (Pages 2326 in you text) 3 Plasma Time Course Log Plot – Not a straight line! Looks like there is a fast phase ( α )and a slow phase ( β ) Time 2 4 6 8 10 12 14 AMOUNT 1 10 100 α β 4 Conceptual Approximation • Fast phase – α – Distribution into peripheral compartment – t ½ for distribution • Slow phase = β – Elimination from the peripheral compart. – t ½ for elimination • Not precisely correct mathematically • (What if distribution is slower than elimination?) 5 It’s the sum of two lines (exponentials) Long times – it’s just the slower phase (elimination), fast phase has petered out Early times – plasma curve is balance of slow and fast phase (both occuring) can strip out the slow phase to reveal the fast phase Time 5 10 15 20 25 30 AMOUNT 1 10 100 α β 6 Initially drug “only” distribution through small Vi (e.g. plasma) slowly drug distributes into the tissues (peripheral comp.) What is V...
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 Fall '07
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 Pharmacology, α β, fast phase

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