Bii / 14A20: Describe the factors affecting drug absorption from the GI tract
14A20: Exam Report
Describe the factors affecting drug absorption from the gastrointestinal tract.
45% of candidates passed this question.
This is a very broad and open question. While a structured approach was useful, a sound knowledge of first principles or even being able to “think on the fly” would have provided candidates witj enough opportunities to generate a pass.
Bii / 14A20: Describe the factors affecting drug absorption from the GI tract
Definition
Drug absorption = movement of drug from site of admin to site where it is measured in the plasma
Drug Factors
1) Drug Solubility + Dissolution Rate
![Solid Drug](https://jennysjamjar.com.au/wp-content/uploads/2020/08/Solid-Drug.png)
- For drug to be absorbed it must first be dissolved in fluid at site of absorption
- Dissolution depends on drug’s solubility, ionisation & SA
2) Rate of Diffusion
![Rate of Diffussion](https://jennysjamjar.com.au/wp-content/uploads/2020/08/Rate-of-Diffussion.png)
- ↑SA = ↑diffusion
- ↓Thickness of diffusion barriers = ↑diffusion
- ↑solubility of molecule = ↑diffusion
- ↓MW of molecule = ↑diffusion
- ↑[ ] gradient = ↑diffusion
3) Drug pKa
- pKa = the pH at which 50% of molecules are ionised & 50% are unionised
- Unionised → important for diffusion through membrane and ∴ absorption
- Ionised → important for solubility
Drug
V. weak acids
pKa
> 8
pH/Site of Absorption
Unionised at all pH
Absorbed along entire length GIT
Drug
Moderately weak acids
Aspirin 3.5
pKa
2.5 – 7.5
pH/Site of Absorption
Unionised @ gastric pH
Ionised @ intestine pH
∴better absorbed from stomach
Drug
Strong acids
pKa
< 2.0
pH/Site of Absorption
Ionised all pH
Poorly absorbed
Drug
V. weak bases
pKa
< 5
pH/Site of Absorption
Unionised at all pH
Poorly absorbed from GIT
Drug
Moderately weak bases
pKa
5 – 11
pH/Site of Absorption
Ionised @ gastric
Unionised @ intestine
∴better absorbed at intestine
Drug
Strong bases
pKa
> 11
pH/Site of Absorption
Ionised at all pH
Poorly absorbed from GIT
4) Disintegration Time of Tablet
- Rapid disintegration time = absorbed quickly
- Slow disintegration time = absorbed slowly
- ∴Manipulated by manufacturers (amount of binder + compression force)
→ A disintegrated drug must dissolve in order for it to be absorbed
5) Drug Size & SA
![](https://jennysjamjar.com.au/wp-content/uploads/2020/08/Ficks-Law-of-Diffussion.png)
- Smaller particle → greater contact b/w solid surface + aqueous solution → higher dissolution rate → ↑absorption
Patient Factors
1) Gastric Emptying
- Drug swallowed → enters stomach
- Needs to be emptied into SI
- Duodenum has greatest absorption capacity
- ∴↑gastric emptying time = slow to reach duodenum & slows absorption
i.e. Penicillin is unstable in acid + decomposed if delayed gastric emptying
2) Intestinal Motility
- Peristaltic movements of duodenum bring drug particles into contact with SI mucosa
- ∴drug must have enough ‘residence time’ in duodenum for absorption
- ↑motility e. diarrhoea = ↓absorption
3) Food + Transit Time
- Presence of food can ↑/↓ absorption depending on drug
- Some food is not always predictable + can have clinical consequences
4) Drug Stability in GIT
- Drugs can be:
- Destroyed by gastric acid = ↓absorption
- Metabolised by GIT enzyme = ↓absorption
5) pH GIT + SA
Month
pH
6.8
SA
Small
Drug Absorbed
Lipophilic, neutral + basic
Stomach
pH
1 – 3
SA
Moderate
Drug Absorbed
Lipophilic, neutral + acidic
SI
pH
5 – 7.5
SA
V. large
Drug Absorbed
MAJOR SITE OF DRUG ABS
LI
pH
7.9 – 8
SA
Small
Drug Absorbed
All drugs, but lesser extent
Rectum
pH
7.5 – 8
SA
Small
Drug Absorbed
All drugs, but lower 1/3 goes direct to systemic circulation
6) Blood Flow
- Drugs absorbed → mesenteric veins → portal v. → systemic circulation
- ∴any ↓BF → ↓absorption
- Author: Krisoula Zahariou