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  • 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