Non-Linear+Kinetics

Non-Linear+Kinetics - Non-Linear Kinetics 1 First Order...

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Non-Linear Kinetics 1
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First Order Rate constants independent of conc, time T ½ independent of conc, time Cl independent of conc, time Linear E.g. doubling dose doubles the plasma conc Loading dose Maintenance dose Infusions 2
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Non-linear What if? Doubling dose 4x blood level? Halving the dose small drop in blood level Big picture Identify the occurrence of such behavior Identify the parameters likely changed Identify/understand the mechanisms 3
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Two Equations, Five Constants The big two equations: LD = C p,0 = F*S*Dose/V D Repeated dose/infusion C pss,avg =R A /Cl or R 0 / Cl The big fundamental parameters: F, ka, V D , Cl R, CL H None of these should change with dose or time (note two-compartment model with changing V D could be considered non-linear) 4
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GI Absorption/Bioavailability Saturable transport in gut wall F, ka Drug limited solubility F, ka (doesn’t dissolve in time) Saturable metabolism In liver (first-pass), F (maybe Cl H ) Could also be in gut, F 5
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Non-Linear+Kinetics - Non-Linear Kinetics 1 First Order...

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