Pharmacokinetics
Definitions
- Pharmacokinetics is the study of the bodily absorption,
distribution, metabolism, and excretion of drugs
- Pharmacodynamics is the study of the biochemical and physiological
effects of drugs and the mechanisms of drug action
- Pharmacokinetics of a drug are dependent on
- Absorption of the drug into the body
- Distribution of the drug throughout the fluids and tissues of the
body
- Metabolism of the drug and its daughter metabolites
- Excretion or elimination of the drug from the body
First order kinetics
- A constant fraction of the drug in the body is eliminated per unit
time
- The rate of elimination is proportional to the amount of drug in the
body
- The majority of drugs are eliminated in this way
- With drugs displaying first order kinetics various properties can be
defined
Clearance
- The apparent volume of plasma from which a drug is entirely removed
per unit time
- Usually expressed in proportion to bodyweight or surface area
Volume of distribution
- The volume into which a drug appears to be uniformly distributed at
the concentration measured in plasma
- Usually a steady state volume of distribution equal to the amount of
drug in the body
- Drugs that are lipid soluble have a high volume of distribution
- Drugs that are lipid insoluble have a low volume of distribution
Half life
- The time taken for the plasma concentration of a drug to fall by 50%
when first-order kinetics are observed
- Many drugs have an initial redistribution phase with a short
half-life (t1/2a)
- Followed by an elimination phase with a longer half-life (t1/2ß)
Bioavailability
- The proportion of a dose of a specified drug preparation entering
the systemic circulation after administration by a specified route
- Usually used to mean “oral bioavailability” which is the ratio of
the areas under the plasma concentration-time curves of intravenous and
oral administration of the same dose of a drug
Multicompartment models
- First order kinetics is often only displayed in drugs that
distribute around a single compartment
- The human body is more complex
- Has several compartments - muscle, blood, brain fat etc
- Some drugs (induction anaesthetic agents) are initially
transported to organs with a rich blood supply
- After a few minute the agent redistributes to other parts of the
body
- Initially the blood concentration rapidly falls due to
redistribution
- Later the blood concentration decreases more slowly due to
elimination of the drug
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