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Pharmacokinetics (PK)
The study of the disposition of a drug
The disposition of a drug includes the
processes of ADME  Absorption
 Distribution
 Metabolism
 Excretion
Elimination
ADME
Importance
Without the knowledge gained from PK
studies, patients may suffer:
 Toxic drugs may accumulate
 Useful drugs may have no benefit because
doses are too small to establish therapy
 A drug can be rapidly metabolized.
Routes Of Administration
Routes Of Drug
Administration
Parenteral
Injection
Topical
Enteral
Respiratory
Rectal
Oral
Absorption
The passage of drug from the site of
administration into the general circulation.
Exception: Intravenous injections
I.V Drug
Immediately
Oral Drug
Delayed
completely
incomplete
The Process
Absorption relies on
 Passage through membranes to reach the
blood
 passive diffusion of lipid soluble species.
Absorption & Ionization
Non-ionised drug
More lipid soluble drug
Diffuse across cell
membranes more easily
Site Of Absorption
Most drugs are absorbed in the small
intestine, because
 It is the portal for absorption of nutrients into
blood
 It is surrounded by a very thin
membrane with a large surface
 area
Rate & Extent
Rate - How rapidly does the drug get from
its site of administration, to the general
circulation?
Extent - How much of the administered
dose enters the general circulation
Distribution
The movement of drug from the blood
to and from the tissues
Plasma Protein Binding
Many drugs bind to plasma proteins in the
blood steam
Plasma protein binding limits distribution.
A drug that binds plasma protein diffuses
less efficiently, than a drug that doesn’t.
Elimination
The irreversible removal of the parent
drugs from the body
Elimination
Excretion
Drug Metabolism
(Biotransformation)
Drug Metabolism
The chemical modification of drugs with
the overall goal of getting rid of the drug
Enzymes are typically involved in
metabolism
Drug
Metabolism
More polar
(water soluble)
Drug
Excretion
Sites of Drug Metabolism
Metabolism occurs in many tissues
E.g. brain, kidney, lung
But mostly in the liver because …
all of the blood in the body passes
through the liver.
Intravenous
Administration
Oral
Administration
Metabolism
Liver
Intestines
Consequences Of Metabolism
Drug metabolism != Drug inactivation
The metabolite may have




Equal activity to the drug
No or reduced activity
Increased activity (Prodrugs)
Toxic properties, not seen with the parent
drug
The Most Important Enzymes
Microsomal cytochrome P450
monooxygenase family of enzymes, which
oxidize drugs
Act on structurally unrelated drugs
Metabolize the widest range of
drugs.
Excretion
The main process that body eliminates
"unwanted" substances.
Most common route - biliary or renal
Other routes - lung (through exhalation),
skin (through perspiration) etc.
Lipophylic drugs may require several
metabolism steps before they are
excreted
ADME - Summary
Pharmacodynamics (PD)
The study of the biochemical and physiological
effects of drugs.
Pharmacokinetics Pharmacodynamics
what the body does
to the drug
what the drug does to
the body.
Drug Interaction
When a drug alters the effects of another
drug
Drug A may alter these factors of drug B:
 Efficiency
 Rate of effect
 Side effects.
Drug Interaction
Pharmacodynamic:
Pharmacokinetic:
The drug effect is altered
Amount of drug in blood
is altered
References
 A First Course in Pharmacokinetics and Biopharmaceutics - available
at http://www.boomer.org/c/p1/
 http://www.le.ac.uk/pa/msc/pklecture.pdf
 http://web.vet.cornell.edu/public/pharmacokinetics/pharmacokinetic
s.html
 The Liver and Drug Metabolism - available at
http://adultpain.nursing.uiowa.edu/MedGen/Liver.htm
 http://www.ttuhsc.edu/pharm/Freeman/med/DrugElim1.ppt
 http://www.bps.ac.uk/epharnet/adme.ppt
 http://www.usask.ca/medicine/pharmacology/Mon11SEP.pdf
 http://www.usask.ca/medicine/pharmacology/Fri08SEP.pdf