Phil Rowe Reader in pharmaceutical computing School of Pharmacy

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Phil RoweReader in pharmaceutical
computingSchool of Pharmacy Chemistry
All these presentations can be downloaded
fromhttp//www.staff.livjm.ac.uk/phaprowe/then
follow 'Nurse prescribing'
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Lecture 2 Routes and patterns of drug
administration
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Part 1Routes of administration
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Routes to be covered

• Intravenous
• Oral
• Buccal Rectal
• Intramuscular
• Subcutaneous
• Topical

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Intravenous

• Advantages
• No absorption stage - immediate effect without
  delay
• Guaranteed 100 bioavailability - no variation
  between patients
• Disadvantages
• Person administering dose needs careful training
• Sterility essential
• Possible extravasation

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Oral

• Advantages
• Simplicity
• Disadvantages
• Low and unpredictable bioavailability for some
  drugs
• Rate of absorption - slow and unpredictable
• Release from the tablet/capsule etc
• Gastric emptying

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Gastric emptying
Drugs absorbed very slowly
Stomach
Small intestine
Drugs absorbed much more quickly
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Drug absorption from oral route

• Absorption may be delayed by
• Disintegration of dosage form (Tablet capsule
  etc)
• Capsules (Soft gelatin) Few minutes
• Capsules (Hard gelatin) Few minutes to an hour
  or more
• Tablets Very variable Several hours for
  controlled release
• Gastric emptying into intestine.
• Liquid 50 in about 30 mins
• Solids 50 in about 2 hours

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Buccal Rectal
Rectal may be useful if patient is
vomiting. Rectal not terribly popular with
British! Both may be useful in increasing
bioavailability.
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Blood drainage from G.I.T.
General circulation
Mouth
Stomach
Small intestine
Large intestine
Liver
Rectum
General circulation
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Buccal Rectal
Both the buccal and the rectal route have the
potential to increase bioavailability by allowing
drugs to bye-pass the liver. Main advantage is
that the dose that will reach the body is more
predictable. Buccal route works well. e.g.
Buccastem (Buccal prochlorperazine - antiemetic)
delivers higher and more predictable dose than
oral route. Rectal is less reliable.
Effectiveness depends on the individual patient
and the exact placing of the dose.
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Intramuscular
Oil or water
Drug
Blood
Rate of absorption of drug may be limited either
by rate of release from injection vehicle or the
ability of the blood to carry the drug away.
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Intramuscular

• Oil based dosage form
• Rate limiting step is release from vehicle. Slow
  (Many hours to a few weeks) but predictable.
• Water based dosage form
• Rate limiting step generally removal of released
  drug by blood flow. Quite quick, but very
  variable - exercise or rubbing the injection site
  will increase rate of dispersal into body.

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Subcutaneous
Drug has to carried away from the injection site
by blood or lymph. Both blood and lymph flows to
the subcutaneous tissue are poor. Release
therefore rather slow. If slow release is wanted,
probably better to use a slow release formulation
(Oil or plastic). Can be painful.
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Topical

• With topical application, intention is generally
  to achieve a local effect. However, in many
  cases, drug will be absorbed into the general
  circulation.
• Examples
• Inhaled steroids intended to act in the lungs,
  but are absorbed and can cause some adrenal
  suppression.
• Beta-blockers in eye-drops reach measurable
  concentrations in blood.

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Part 2Patterns of administration
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Patterns to be covered

• Single dose
• Intravenous infusion
• Multiple dose

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Single dose
Rapid release - Useful for a "Quick hit". e.g.
pain killers.
Slow release - Useful where we want a prolonged
steady exposure to the drug
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Intravenous infusion
Css
Steady state
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Intravenous infusion
Rate of infusion
Concentration at steady state (Css)

Clearance
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Use of a loading dose
Immediately effective treatment
Therapeutically effective range
With loading dose
No loading dose
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Multiple dose
with and without accumulation
Much of previous dose still present
Previous dose almost fully eliminated
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Concentrations at Steady State
Peak
Average
Trough
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Multiple dosing
Bioavailability x Dose size
Average Conc

Clearance x Dosage interval
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Divided doses
2 x 300 mg
6 x 100 mg
3 x 200 mg
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Divided doses
Dose division should be great enough to ensure
that peaks and troughs are not excessively
high/low. But, always keep number of doses per
day as low as possible to maximise compliance.