TBD

1

• Pharmacokinetics

2
Pharmacokinetics (PK)

• The study of the disposition of a drug
• The disposition of a drug includes the processes
  of ADME -
• Absorption
• Distribution
• Metabolism
• Excretion

3
ADME
4
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.

5
Routes Of Administration
Routes Of Drug Administration
Enteral
Parenteral
Oral
Injection
Rectal
Respiratory
Topical
6
Absorption

• The passage of drug from the site of
  administration into the general circulation.
• Exception Intravenous injections

I.V Drug Oral Drug
Immediately Delayed
completely incomplete
7
The Process

• Absorption relies on
• Passage through membranes to reach the blood
• passive diffusion of lipid soluble species.

8
Absorption Ionization
Non-ionised drug
More lipid soluble drug
Diffuse across cell membranes more easily
9
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

10
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

11
Distribution

• The movement of drug from the blood to and from
  the tissues

12
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 doesnt.

13
Elimination

• The irreversible removal of the parent drugs from
  the body

Elimination
Drug Metabolism (Biotransformation)
Excretion
14
Drug Metabolism

• The chemical modification of drugs with the
  overall goal of getting rid of the drug
• Enzymes are typically involved in metabolism

Metabolism
More polar (water soluble) Drug
Excretion
Drug
15
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.

16
Intravenous Administration
Oral Administration
Liver
Metabolism
Intestines
17
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

18
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.

19
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

20
ADME - Summary
21
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.
22
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.

23
Drug Interaction
Pharmacokinetic Amount of drug in blood is
altered
Pharmacodynamic The drug effect is altered
24
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
  /pharmacokinetics.html
• The Liver and Drug Metabolism - available at
  http//adultpain.nursing.uiowa.edu/MedGen/Liver.ht
  m
• 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