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Pharmacokinetics
Foundations of Biomedical Science 1
King's College London
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Terminology Pharmacokinetics (PK) - What the body does to the drug Pharmacodynamics (PD) - What the drug does to the body PK/PD - Relationship between the two
Zero Order Kinetics Drug is cleared by a pump
Alcohol, phenytoin are zero order drugs, and can accumulate
First Order Kinetics Drug is emptied by a tap Rate of reaction is not only dependent on k, but also instantaneous concentration of the drug
Most drugs follow first order kinetics and tend to not accumulate in the plasma Once they are absorbed, they will move into another compartment of the body Two compartment models cause biphasic decline
Pharmacokinetics
Friday, 1 February 2019 14:
Half-life Time taken for plasma concentration of A to fall by half For a monoexponential decline, half life can be estimated anywhere on the curve between two points
T1/2 = 0/k
Elimination Rate Constant (k) Rate of change is related to elimination rate constant (k) and concentration at time t Converting to natural logarithms will give a straight line plot, making the gradient equal to the elimination rate constant
ADME Absorption Usually means oral administration Process by which drug moves from site of administration to site of action Quantified as absorption rate constant (first order process) Absorption can be solubility (dissolution rate) and pH (pKa) dependent Distribution Volume of distribution (Vd) is not a real volume, but how the amount of the drug in the plasma relates to the initial amount of drug given Vd = Dose A/A 0 Metabolism Phase I: When drugs are modified by enzymes, usually in the liver, to make it more water soluble Phase II: Conjugation reactions, where body binds a water soluble conjugating group to make the drug more water soluble Excretion Clearance - Volume of plasma cleared of drug per unit time, Cl = k x Vd , usually 1/min Can be limited by blood flow from organs Can include saturable processes, metabolism and excretion Clearance = Liver blood flow x Extraction ratio (Eh)
Renal Clearance Renal Eh x Renal blood flow
Pharmacokinetics
Module: Foundations of Biomedical Science 1
University: King's College London
