Absorption

[SH4:p8]

 

=== Unfinished ===

More notes on sublingual

PR paracetamol and indocid

===

 

Systemic absorption of drug (regardless of route) depends on:

• Solubility of the drug
• Blood flow to the site
• Area of surface available for absorption

Oral administration

Most absorption occur in small intestine due to greater surface area

Advantages

• Convenient
• Economical

Disadvantages

• Emesis caused by irritation of GIT mucosa
• Destruction of drug by enzymes or gastric acid
• Irregularities in absorption (also influenced by presence of food)
• Potential metabolism by enzyme or bacteria in GIT

First-pass hepatic effect

• Drug absorbed from GIT goes into portal venous blood
  --> Goes through liver
  --> Drugs undergo hepatic metabolism before going into systemic circulation

 

Oral transmucosal administration

• Sublingual or buccal route permits rapid onset due to bypassing of hepatic metabolism
• Sublingual area drains directly into SVC
  * e.g. GTN
• Nasal mucosa - also an effective route (?? bypass hepatic metabolism)

Rectal administration

• Superior hemorrhoidal vein drains into portal venous system
• Lower rectal area drains directly into systemic circulation (bypassing liver)
• [???] Dentate line = cut off
• Drugs absorbed from suppositories in the lower rectum go into inferior vena cava
  --> Bypass the liver [BGK9:p43]

Transdermal administration

• Rate-limiting step in absorption
  --> Diffusion across stratum corneum of the epidermis

 

Examples:

• Scopolamine
• Fentanyl
• Clonidine
• Nitroglycerin
• Oestradiol
  * [Examiner's report 1996A13]
  * [???]

 

NB:

• Postauricular zone has thin epidermal layer and slightly higher temperature
  --> The only site where scopolamine is absorbed transdermally predictably

Advantages

• Sustained therapeutic plasma concentration
• Lower incidence of side effects (due to lower dosage used)
• Enhanced compliance

 

Disadvantages

• Contact dermatitis
• 7 days limit for one application
  * Due to sloughing of stratum corneum
• Tolerance for some drugs
  * e.g. scopolamine and nitroglycerin
• Slow onset [???]
• Transdermal preparation requires special formulation

Factors influencing transdermal absorption

Transdermal absorption is increased where:

• High combined water and lipid solubility
• MW < 1000
• pH 5-9 in a saturated aqueous solution
• absence of histamine-releasing effects
• Daily dose requirement < 10mg

 

Other factors which may influence absorption

• Blood flow
• Body site (determines the thickness of the epidermal layer)
• Skin temperature
• Skin integrity
• Ethnic group [???]
• Age [???]

 

 

Tolerance

• Sustained plasma concentration provided by transdermal administration of scopolamine and nitroglycerin can lead to tolerance