Factors Impacting Oral Absorption Flashcards
(28 cards)
What is absorption?
movement of drugs from site of admin to systemic circulation
- variability in the rate + extent of A from SoA has influence on drug effect
T or F: Bioavailability is a measure of rate of drug exposure
F - measure of extent
What limits drug absorption via IM or SC routes
Perfusion limited (BF to the site)
- requires movement through or around cells of the capillary wall
- permeability is not an issue for small molecules
peak happens earlier than oral
passive diffusion: types + what uses them
Principle: driven by conc gradients
- BF: makes good sink conditions (maintain gradient)
transcellular (through cell): small, unionized, moderately lipophilic
paracellular (bw cells): macromolecules + hydrophilic molecules
Active transport
saturable process that uses energy (goes against conc gradient)
- bind to transporter (OAT, OCT) + gets moved across
used for organic anions (-), cations (+) + drugs that look like endogenous substrates
Efflux: PGP
impacts oral absorption
- pumps shit back into intestinal lumen (decreases A)
What are the 3 main categories impacting oral absorption
1) Physio of GI: SA, BF, pH, transit time
2) Drug traits
3) Dosage Form: only one we can really change + do much about
Physiology of stomach
low pH (1-3) : WB are ionized here, WA unionized
- may help with dissolution of some drugs
small SA, low perfusion + fast transit time (30 mins)
- delays in gastric emptying (increase in TT): impact drug delivery to target site
NOt common site for drug absorption
Main Fxn of Stomach
process + transport food
- time it takes to empty stomach depends on meal + volume
——- large or fatty: increase time + delay delivery
General: rate of A is highest when taken with no food just glass of water (10mins)
T or F: food delays gastric emptying
generally yes; extent varies based on type of food and how much
- also varies based on drug
Duodenum
site of most of drug A
-short (20cm)
- pH: 6
- rapid transit time
- big SA : villi + microvilli
- good perfusion : good sink conditions
Rectum A
limited absorption; can be useful if can’t take drug by mouth
—- lower peak C + AUC (extent)
—low SA, fluid V, stirring capacity , and variable retention time
Two main sections of drug traits
Permeability
Solubility
What impacts ability of drug to cross membranes?
SA, conc gradient, and permeability
- permeability is fxn of molecular size, lipophilicity, and degree of ionization
—— increase in MW, decrease in permeability
—- more lipophilic, increase permeability
BCS Class 2
high P + low S
oral A may be acceptable for most but may need to do some changes
- may need to make adjustments to increase solubility
BCS Class 1
high S + P
ideal drugs; excellent A
eligible for biowaiver based on acceptable dissolution test (not bio equivalence study)
BCS Class 3
low P + high S
oral A may be okay
BCS Class 4
low S and P
- can’t be admin orally without the development of extensive + complex formulations
Dosage Form traits
particle size, modifications of form that change dissolution, solubility + drug release
- decrease PS: increase SA + increase solubility
What is the most common rate limiting step for oral drugs
dissolution : moving into fluid before A
—- seen more in tabs + caps
What is a dissolution test
standardized test + procedure that predicts A and F of drugs
- good especially for class I
Why would you use DF to delay or slow A
- in order to get optimal P conc
Ex// MR or DR drugs (zero order)
help extend dosing/ less frequent dosing (good for drugs with short t1/2) + may help decrease fluctuation in C
** can cause terminal phase to be A limited though
4 ways food can impact A and F
1) decrease rate
2) decrease extent
3) increase rate
4) increase extent
Mech of food decreasing rate
slows A via slowing gastric emptying (stops it from reaching target SoA)
—- most common way
