Pharmacokinetics describes the processes the body undergoes to metabolize and eliminate drugs, including absorption, distribution, metabolism, and excretion. Drugs can be administered topically, systemically, or directly to their target area. Orally administered drugs must dissolve and be absorbed through the stomach and intestines before entering systemic circulation. Some drugs are metabolized in the liver before circulating systemically, resulting in reduced bioavailability. Drugs can also be administered rectally but have disadvantages like slower absorption and potential irritation. A drug's absorption and distribution depend on its properties and formulation.

1. Pharmacokinetics/
Pharmacokinetic principles
By
C Settley
Compiled by C Settley

2. Pharmacokinetics of drugs p29 (definition)
• It is the effect of the body on the drug molecules
over time through the following processes:
• Absorption
• Distribution
• Metabolism (bio-transformation)
• Elimination /excretion
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3. Pharmacokinetics
• Topical delivery- application to body areas where they
exert localised effects. Eg a cream/lotion. These drugs do
not require absorption into the systemic blood
circulation to be effective.
• Systemic drugs- need to be administered in such a way
as to allow them to be absorbed into the systemic blood
circulation.
• Some drugs are administered directly into their target
areas.
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4. Compiled by C Settley

5. Oral route
• Dissolves- enters the bloodstream- hepatic portal
circulation- systemic circulation.
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6. The oral route
• All oral medication are dissolved in the lumen of the
GIT. Most dissolve in the stomach, unless formulated
to disintegrate and dissolve further down in the
alimentary canal.
• The stomach cannot be regarded as an absorption
organ but may allow some of the dissolved drug
molecules to enter into the bloodstream. The small
intestine is the primary site of the absorption of
drugs.
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7. The oral route
• From the stomach and small intestines, drug molecules have
to cross biological membranes to reach the hepatic portal
circulation.
• Blood entering the portal circulation then moves through the
portal vein, liver, inferior vena cava, right side of the heart,
pulmonary circulation and the left side of the heart before
finally entering the systemic circulation, from where absorbed
drug molecules will be distributed to other parts of the body.
• Per oz, per os, PO, peroral, per mouth
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8. Compiled by C Settley

9. First pass metabolism- pg31
• The first-pass effect (also known as first-pass metabolism or pre
systemic metabolism/elimination) is a phenomenon of drug
metabolism whereby the concentration of a drug is greatly reduced
before it reaches the systemic circulation. It is the fraction of drug
lost during the process of absorption which is generally related to
the liver and gut wall.
• After a drug is swallowed, it is absorbed by the digestive system and
enters the hepatic portal system. It is carried through the portal
vein into the liver before it reaches the rest of the body. The liver
metabolizes many drugs, sometimes to such an extent that only a
small amount of active drug emerges from the liver to the rest of
the circulatory system. This first pass through the liver thus greatly
reduces the bioavailability of the drug.
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10. Compiled by C Settley

11. Rectal route (per rectum, PR)
• Unpopular & uncomfortable
• Indications for this route?
• Absorptive surface of the rectum is small.
• Results in slowed rate of rectal absorption.
• The rectum is drained by three veins: superior,
middle and the inferior rectal veins .
• The inferior and middle rectal veins drain the
lower part of the rectum, while the superior rectal
vein drains the upper part.
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12. Rectal route (per rectum, PR)
• Drugs administered into the proximal rectum are
subjected to first-pass metabolism. However, drugs
administered from a low rectal site reach the general
circulation without first passing through the liver.
• Additionally, some drugs can cause irritation of the
rectal mucosa. Informed consent must be sought
prior to administration of any rectal preparation
especially if given during general anaesthesia.
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13. The disadvantages associated with
administration of drugs rectally include:
• (a) interruption of absorption by defecation, which may
occur particularly with irritant drugs;
• (b) the surface area of the rectum is far smaller for
absorption than that of the duodenum;
• (c) the fluid contents of the rectum are much smaller than
those of the duodenum and this may produce problems
with dissolution of some drugs;
• (d) degradation of some drugs by micro-organisms may
occur in the rectum;
• (e) patient acceptability may be a problem
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14. Systemic bioavailability (pg 42)
• This is the percentage of the oral drug that actually
reaches the systemic blood circulation
• Only a fraction of an oral drugs dosage actually reaches
the systemic blood circulation
• Reasons for this include:
– Not all drug molecules are absorbed from the GIT
– First pass effect
• The liver may eliminate a significant portion of the drug.
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15. Absorption (pg36)
• Absorption is the movement of a drug into the bloodstream.
• Drug absorption is determined by the drug’s physicochemical
properties, formulation, and route of administration.
• Dosage forms (eg, tablets, capsules, solutions), consisting of
the drug plus other ingredients, are formulated to be given by
various routes (eg, oral, buccal, sublingual, rectal, parenteral,
topical, inhalational).
• Regardless of the route of administration, drugs must be in
solution to be absorbed.
• The easier it crosses plasma membranes the more readily it
will be absorbed.
• The intravenous route bypasses this stage.
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16. Absorption
Compiled by C Settley

17. Absorption: The plasma membrane
• The barrier between:
• Intracellular and
• Extracellular fluid
• The barrier may be crossed by:
• Diffusion (the spreading of something more widely)
• Active transport (the movement of ions or molecules across a cell
membrane into a region of higher concentration, assisted by enzymes and
requiring energy)
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18. Absorption: properties of the drug molecule
Certain properties of the drug molecules will determine their
ability to cross the membrane
• Lipid solubility
– More lipid soluble drugs cross cell membranes more easily
• Size of the drug molecules
– Smaller molecules cross more easily
• Ionisation of the drug molecules
– Unionised molecules cross cell membranes more easily (Ionization is
the process by which an atom or a molecule acquires a negative or
positive charge by gaining or losing electrons to form ions, often in
conjunction with other chemical change)
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19. Distribution (pg 42)
• The systemic blood circulation transports the drug molecules to
other parts of the body.
• The molecules then leave the blood stream (capillaries) at their
sites of action to enter other fluid compartments of the body.
• Organs that receive the greatest percentage of cardiac output
receive the greatest percentage of the absorbed drug.
• In other words after a drug enters the systemic circulation, it is
distributed to the body's tissues. Distribution is generally uneven
because of differences in blood perfusion, tissue binding (eg,
because of lipid content), regional pH, and permeability of cell
membranes
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20. Drug elimination- pg 43
• Drug action may be terminated by:
• Biotransformation (Biotransformation is the process whereby a substance is
changed from one chemical to another (transformed) by a chemical reaction
within the body. Metabolism or metabolic transformations are terms frequently
used for the biotransformation process)
• Excretion (Excretion is the process by which waste products of metabolism and
other non-useful materials are eliminated from an organism)
• Redistribution (reversible transfer of drug from one location to another within the
body)
• Tolerance (Tolerance is a person's diminished response to a drug, which occurs
when the drug is used repeatedly and the body adapts to the continued presence
of the drug. Resistance refers to the ability of microorganisms or cancer cells to
withstand the effects of a drug usually effective against them)
Compiled by C Settley

21. Metabolism- pg 44
• The liver is the primary responsible organ for
biotransformation
• Other tissues participate in metabolism:
• Lungs
• Kidneys
• Skin
• Adrenal cortex
• Brain
• Gastrointestinal tract
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22. Excretion (pg47)
• Drugs may be excreted via:
• The lungs
• Gastrointestinal tract & liver
• Kidneys
• Saliva, tears, perspiration
• A drug’s concentration is highest in the organ that
excretes it.
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23. Applied pharmacokinetics (pg 48)
• Elimination half life (t½)
• The amount of time for the drug’s plasma
concentration to be reduced by 50%
• Half life of a drug may be prolonged by kidney / liver
failure / aging.
• Used to determine dosage interval
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24. Applied pharmacokinetics
• Loading dosages
• A loading dosage /bolus is given to obtain the
required therapeutic effect more rapidly
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25. Applied pharmacokinetics
• Maintenance dosages
• Are given at regular intervals
• To reach and maintain the desired constant
therapeutic levels (steady state concentration)
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26. Applied pharmacokinetics
• Therapeutic index
• The difference between the minimum plasma concentrations
of the drug
• At which it is effective
• And at which it is toxic
• The therapeutic index indicates a drug’s margin of safety
• Drugs with a narrow therapeutic index reach toxic levels very
easily
• E.g: warfarin, theophylline, phenytoin
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27. Medicine administration
• The 5 R’s of medication administration
– Right patient
– Right medication
– Right dose
– Right time
– Right route
NB. Medication administration done under the
supervision of a R/N (R2598)
Compiled by C Settley

28. References
• http://www.rch.org.au/neurology/patient_informati
on/antiepileptic_medications/
• Youtube videos: Handwritten Tutorials
Compiled by C Settley