knipp lecture Flashcards
mouth to anus transit time
24-32 hours
small intestinal transit time
3 hours
most absorption occurs where
small intestine
small intestine pH
5-6.5
colon drug absorption mainly occurs in what region
ascending region
characteristics of intestine
- most transporters in SI
-upper SI= mixing
-lower SI= electrolyte
-colon= fluid electrolyte absorption
stomach compartments
- fundus (gas)
-body (storage) - antrum-lowest part of stomach
oral cavity epithelia
stratified squamous epithelium
esophagus epithelium
stratified squamous epithelium
trachea epithelia
pseudostratified squamous
stomach epithelium
columnar epithelial cells
large and small intestines
columnar epithelial cells
lower rectum epithelia
stratified squamous non-keratinized to keratinized
upper rectum epithelia
simple columnar
solute carrier (SLC)
-43 subfamilies
->300 members
-generally influx or secretory efflux transporters
-PepT1, OATs, OATPs
ATP-binding cassette (ABC)
-7 subfamilies
-50 members presently identified
-generally efflux-multidrug resistant transporters
-p-glycoprotein MRP
passive paracellular permeation
-hydrophilicity
-molecular size and shape
-pka of ionizable groups
-linear increase in permebility with increasing concentrations
-adjuvants can open tight juntions and increase transport
routes of permeability
-influx transporter mediated
-passive transcellular
-passive transcellular and efflux
-passive paracellular
-metabolism
-efflux of the metabolites
facilitative/ active transcellular permeation
- affinity(Km) Capacity (Vmax/Jmax)
-concentration dependent saturation
-expression level
-function
-excipients
sites of drug metabolism
first pass: GI epithelium/ liver
systemic metabolism: can occur in organs and in the blood stream
