9-Absorption

Question 1

Bioavailability

F

Answer 1

F = F_A x F_G x F_H

F = fraction of oral dose that reaches systemic circulation

A = Fraction absorbed

G = GI, fraction of drug that survived intestinal extraction

H = Hepatic, fraction of drug that survived hepatic extraction

Question 2

Small Intestine

Answer 2

Major site of drug absorption

due to large surface area (200m²)

Villi

pH = 6-7

transit time is about 3 hours

Question 3

Mechanisms of Absorption

Answer 3

• Simple (Passive) Diffusion
• Carier Mediated Facilitated Diffusion
• Active Transport

Question 4

Dissolution

Answer 4

can be rate limiting step in absorption

• Noyes & Whitney formula for rate of dissolation
  
  • Solubility of Drug
  • Surface Area
    
    • Small particle size increases surface area
  • Thickness of unstirred layer
  • Better water solubility
    
    • drug specific property but can be modified
    • –> salt form (HCl)

Question 5

Dissolution:

Water Solubility

Answer 5

better water solubility better dissolution

• Water solubility of drugs are influenced by the pH in the gut
  
  • Acids = more soluble in BASIC conditions
  • Basis = more soluble in ACIDIC conditions

Question 6

Factors Affecting Oral Absorption

Answer 6

• Physiological Factors
  
  • Gastric Emptying Time
  • Intestinal Transit time
• Physicochemical properties of drug that impact permeability
  
  • Molecular Size
  • LipoPHILICITY
• ​

Question 7

Physiological Factor that effects absorption:

Gastric Emptying

Answer 7

• ACCELERATED BY:
  
  • ​Liquid
  • Prokinetic Drugs
• ​DELAYED BY
  
  • ​Food, Migraine
  • Diabetic gastroparesis
  • ANTICHOLINERGIC DRUGS
• ​Effect of Gastric Emptying vary depending on drugs
  
  • Rapid dissolution in stomach
    
    • ​INCREASEDgastric emptying rate ->quickens drug absorption
    • Ex. ibupropfen / acetaminophen
  • Rapid Dissolution in intestine
    
    • ​INCREASEDgastric emptying ->quickens drug absorption
    • Ex. enteric coated products (omeprazole)
  • POOR dissolution drugs
    
    • ​DELAYED gastric emptying –> INCREASE extent of drug absorption

Question 8

Gastric Emptying/Intestinal Motility:

Poor Dissolution Drugs

Answer 8

• DELAYED gastric emptying > SLOW oral absorption
  
  • > INCREASE (possibly) extent of drug absorption
• *DEPENDS ON THE DRUG
  
  • Poor Dissolution Drug = DIGOXIN
    
    • + Prokinetic drug (increase GI motility, metoclopramide)
      
      • > DECREASE in Digoxin level
    • • Anticholinergic drug (decrease GI motility, propantheline)
        
        • > INCREASE in Digoxin Level
        • more time for DIGOXIN to be absorbed in GI

Question 9

Physiological Factor that effects absorption:

Intestinal Motility

Answer 9

• ACCELERATED by:
  
  • Diarrhea / IBS
  • Prokinetic Drugs
• ​DELAYED by:
  
  • ​Contipation
  • Diebetic autonomic Neuropathy
  • ANTICHOLINERGIC DRUGS

Question 10

Oral Absorption:

Physiochemical Properties that impact PERMEABILTY

Answer 10

• Molecular size
  
  • Larger molecules show SLOW diffusion rates
• Lipophilicity
  
  • ​MORE lipophylic compounds show better absorption
  • LARGER logP = MORE lipophilic
    
    • Increase solubility
  • *PRODRUG
    
    • approach to improve lipophilicity
    • Esterase converts prodrug into the active drug

Question 11

BCS Class 2

Answer 11

slow dissolution

Rapid permeation

~33% of marketed drugs

Question 12

BCS Class 3

Answer 12

RAPID dissolution

slow permeation

~21% merketed drugs

Question 13

BCS Class 4

Answer 13

• slow dissoluition*
• slow permeation*

~6% marketed drugs

*all diuretics

and -inavirs (antivirals)