L30/1 - physiological factors affecting drug absorption after oral administration

• anatomy/histology • physiology • pathology • drug interactions • food (fed vs fasting) • GI transit • metabolism within GI • first pass effect in liver • enterohepatic recycling • active secretion

area of concentration you need to be in for efficacy of the drug. most drugs have wide window (e.g 1 paracetamol treats us)

• stomach grinds food and breaks it up by chemical decomposition • gastric fluid is an acid containing pepsin: which can degrade drugs • drug absorption across stomach wall does not contribute much to oral absorption of drugs (drugs mostly absorbed in SI)

• some drugs are degraded by acidic conditions in stomach • so gastro resistant dosage forms that do not release drug in acidic environment have been made • polypeptides are completely degraded by pepsin • so oral route of administration impossible and alternative found (e.g insulin administered by injection)

stomach gradually releases its contents into SI

• meal volume: bigger meal = quicker initial emptying rate • type of meal • physical state of contents • chemicals • drugs • body position • disease • exercise

• fatty acid reduces emptying rate (more carbons on chain = more reduce) • triglycerides reduce emptying rate (occurs in unsaturated more) • carbs and a.a reduce emptying rate (concentration dependent matter/ osmotic pressure)

solutions or suspensions of small particles empty quicker than chunks of material

• acids reduce • alkalis increase

anticholinergics, narcotics, ethanol reduce emptying rate

lying on left side reduces emptying rate

ulcers reduce emptying rate

vigorous exercise reduces emptying rate

• drug in solution in stomach • in fasting subject, the drug leaves stomach rapidly via pylorus

• it cannot pass pylorus • only particles of few mm diameter exit • need to wait for HOUSE KEEPER WAVE: strong contraction • lag time (as nothing has been dissolved) between the moment at which the drug is taken and its arrival at its absorption site

• microvilli of intestinal mucous membrane increase SA • pH of intestinal fluid is neutral / kinda alkaline • SI is where most drugs absorbed

• rate of disaggregation and dissolution • GI transit • transport across GI memb

highly soluble, highly permeable: easiest to work with

poorly soluble, highly permeable: sol can be increased by excipients, changing packet size of drug

highly soluble, poorly permeable

poorly soluble, poorly permeable: hardest to work with

change drugs structure: pro drugs

• antibiotic with poor oral bioavailability (poor permeability) • bacampicillin is ester of this • phyiscochemical properties of bacampicllina low easier passage across intestinal barrier

• HCL: degrades some drugs, but gastro resistant coatings used to protect drug + delay release • pepsin: destroys polypeptides (small peptides survive)