Absorption

• Systemic absorption depends on a drug's solubility, regardless of route of administration
• Local conditions alter solubility, especially in the GI tract
• Blood flow to the absorption site is also important in the rapidity of absorption
• Area of absorbing surface available for drug absorption also determines entry into the circulation

Oral Administration

• The most convenient and economic route of administration
• Disadvantages:

• Emesis caused by irritation of the GI mucosa by the drug
• Destruction of the drug by the digestive enzymes or acidic gastric fluid
• Irregularities in absorption in the presence of food/other drugs
• Metabolism by enzymes/bacteria in the GI tract before systemic absorption can occur

• Onset of drug effect largely determined by rate of GI absorption
• Most absorption occurs within the small bowel due to its large surface area
• Changes in pH of GI fluid promoting a non-ionized form of a drug favors systemic absorption:

• Stomach is acidic, small intestine is alkaline therefore different regions of absorption are favored depending on the drug

• First-Pass Hepatic Effect - drugs from GI tract enter the portal venous blood and pass through the liver before entering the systemic circulation - first pass hepatic effect

• The reason for large differences in the pharmacologic effect between oral and IV doses of some drugs

Oral Transmucosal Administration

• Rapid onset of effect by bypassing liver first pass metabolism
• Venous drainage from the sublingual area passes directly into the superior vena cava
• Buccal administration is another option - better tolerated and less likely to stimulate salivation
• Nasal mucosa can also be used

Transdermal Administration

• Provides sustained therapeutic plasma concentrations of a drug, decreases likelihood of loss of therapeutic effect due to peaks and valleys of injection/oral administration
• Physical characteristics of drugs favouring transdermal absorption:

• Combined water and lipid solubility
• Molecular weight < 1000
• pH 5 - 9 in a saturated aqueous solution
• No histamine releasing effects
• Daily dose <10mg

• Absorption occurs along sweat ducts and hair follicles functioning as diffusion shunts
• Rate limiting step is diffusion across stratum corneum
• Differences in thickness and chemistry of the stratum corneum at different anatomical sites affect absorption
• 7 days is the limit of duration due to regeneration of the stratum corneum
• Contact dermatitis occurs in many patients

Rectal Administration

• Drugs administered into the proximal rectum are absorbed via superior haemorrhoidal veins and transported via the portal venous system to the liver
• Drugs administered in the lower rectum reach systemic circulation without first passing through the liver
• This causes unpredictable responses

Parenteral Administration

• Absorption via subcut/IM injection is more rapid and preidctable than oral administration
• Rate of absorption is more rapid and predictable than after oral administration
• Less irritating and even more rapidly absorbed still if injected into a vein