Pharmacokinetics, Pharmacy, year 2
Lecture 7
Chapter 7: Physiology absorption, Christoffer Aberg
Learning outcomes:
- describe the mechanisms underlying absorptionabsorption rate constant and BA
- discuss the connection between absorption and the relevant pharmacokinetic parameters;
- work out the effect of changes to physiological and pathological processes on the
pharmacokinetic parameters relevant to absorption.
Outline: Solid vs Liquid preparations
Solid (tablet, capsules)
- Dissolution
- Absorption in liquid phase
Liquid
- Direct absorption
Absorption from different administration sites
- Gastrointestinal (GI) permeability limited
- Intramuscular/subcutaneousPerfusion limited (briefly in lecture)
Bioavailability determined by:
With PHPH hypothesis from PTB1
A solid preparation absorbed when in liquid phase
Lecture started from here:
, - Ph difference in oral administration
- (Small) intestine highest surface area, permeability and blood perfusion(small)
intestine main absorption site
Gastric emptying can control absorption rate
- Can be affected by:
o Empty stomach
o Food, especially fat
o Drugs
Permeability-surface area product decreases across intestine
- For permeable molecules small intestine major absorption site
- Ditto for less permeable
, Competing GI reactions:
- Non-enzymatic
- acid hydrolysis (stomach) can destroy drug because this is happening
- Enzymatic
- digestive enzymes (bile, pancreatic fluids)
- metabolic enzymes (intestinal epithelium)
- microflora enzymes (mainly large bowel)
- Complexation with other drugs taken other drugs
- Adsorbents (e.g., charcoal) like an overdose of a drug
Can deal with this by coating the drug
- Or convert the drug to what you want via one of those reactions if you can’t beat them
join them
First pass loss:
- Certain drugs are lost in liver and cannot reach target site since the BA is too lowfirst
pass loss
- Drug must pass through gut wall and liver before reaching systemic circulation properly
Lecture 7
Chapter 7: Physiology absorption, Christoffer Aberg
Learning outcomes:
- describe the mechanisms underlying absorptionabsorption rate constant and BA
- discuss the connection between absorption and the relevant pharmacokinetic parameters;
- work out the effect of changes to physiological and pathological processes on the
pharmacokinetic parameters relevant to absorption.
Outline: Solid vs Liquid preparations
Solid (tablet, capsules)
- Dissolution
- Absorption in liquid phase
Liquid
- Direct absorption
Absorption from different administration sites
- Gastrointestinal (GI) permeability limited
- Intramuscular/subcutaneousPerfusion limited (briefly in lecture)
Bioavailability determined by:
With PHPH hypothesis from PTB1
A solid preparation absorbed when in liquid phase
Lecture started from here:
, - Ph difference in oral administration
- (Small) intestine highest surface area, permeability and blood perfusion(small)
intestine main absorption site
Gastric emptying can control absorption rate
- Can be affected by:
o Empty stomach
o Food, especially fat
o Drugs
Permeability-surface area product decreases across intestine
- For permeable molecules small intestine major absorption site
- Ditto for less permeable
, Competing GI reactions:
- Non-enzymatic
- acid hydrolysis (stomach) can destroy drug because this is happening
- Enzymatic
- digestive enzymes (bile, pancreatic fluids)
- metabolic enzymes (intestinal epithelium)
- microflora enzymes (mainly large bowel)
- Complexation with other drugs taken other drugs
- Adsorbents (e.g., charcoal) like an overdose of a drug
Can deal with this by coating the drug
- Or convert the drug to what you want via one of those reactions if you can’t beat them
join them
First pass loss:
- Certain drugs are lost in liver and cannot reach target site since the BA is too lowfirst
pass loss
- Drug must pass through gut wall and liver before reaching systemic circulation properly
