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
  • 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
  • ↑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

  • 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