Pharmacology
Factors affecting ADME
1. Learning outcomes
Compare the intrinsic and extrinsic factors that can impact upon how a drug interacts with the
body
Explain the rationale behind steps that can be taken to reduce the risk of adverse effects or loss
of efficacy in a drug
Describe the potential (and current limitations) of personalised medicine
2. The “Peter perfect” principle
There are a set of ‘rules’ to calculate how the body will deal with any drug
Why then do all drugs not work in the same way in all people?
- Drugs are designed to the rules
- Sometimes the rules change!
u Extrinsic Factors (Environmental and Drug-induced)
u Intrinsic Factors (Pharmacogenetics)
- Drug design must take into account this ‘wobble’ in the rules
Variation can occur at all stages of ADME
3. Absorption
Formulation - ‘Wrapping’ for the drug
- Site of action
- Time release drugs
Food in Stomach
- Generally, decrease absorption
- Light food can increase absorption
Gastric pH can alter degree of disassociation
Gastric Motility - Has to stay in stomach long enough to be absorbed!
G.I. Tract integrity – Damage to GIT may affect the composition of the membranes and hence the
efficiency of absorption
4. Distribution
Plasma protein binding
Amount of plasma protein varies
between individuals
Binding varies between drugs
Polypharmacy (Warfarin and
phenylbutazone)
Tissue blood flow
Drug must get to site of
absorption
Disease state
Heart condition
Adipose tissue
Drug distributes into AT
Varies enormously between
people (3-50+%)
Amount of drug ‘lost’ also varies
Factors affecting ADME
1. Learning outcomes
Compare the intrinsic and extrinsic factors that can impact upon how a drug interacts with the
body
Explain the rationale behind steps that can be taken to reduce the risk of adverse effects or loss
of efficacy in a drug
Describe the potential (and current limitations) of personalised medicine
2. The “Peter perfect” principle
There are a set of ‘rules’ to calculate how the body will deal with any drug
Why then do all drugs not work in the same way in all people?
- Drugs are designed to the rules
- Sometimes the rules change!
u Extrinsic Factors (Environmental and Drug-induced)
u Intrinsic Factors (Pharmacogenetics)
- Drug design must take into account this ‘wobble’ in the rules
Variation can occur at all stages of ADME
3. Absorption
Formulation - ‘Wrapping’ for the drug
- Site of action
- Time release drugs
Food in Stomach
- Generally, decrease absorption
- Light food can increase absorption
Gastric pH can alter degree of disassociation
Gastric Motility - Has to stay in stomach long enough to be absorbed!
G.I. Tract integrity – Damage to GIT may affect the composition of the membranes and hence the
efficiency of absorption
4. Distribution
Plasma protein binding
Amount of plasma protein varies
between individuals
Binding varies between drugs
Polypharmacy (Warfarin and
phenylbutazone)
Tissue blood flow
Drug must get to site of
absorption
Disease state
Heart condition
Adipose tissue
Drug distributes into AT
Varies enormously between
people (3-50+%)
Amount of drug ‘lost’ also varies
