Drug absorption and Bioavaliability Flashcards
is intramuscular intravascular or extravascular
extravascular
for drugs administered extravacularily, do they act systemically or locally?
systemically
if drugs are intended for local use, what can be a concern?
systemic absorption
define bioavailability?
refers to the extent of absorption of intact drug. Fraction of an extravascularly administered dose that reaches the systemic circulation intact
what is bioavaliability important for?
knowing the dosage of drug, if poor bioavailability, you will increase the dose
when is absolute bioavailability used?
with reference to an intravenous dose- if you give it IV, you have 100% absorption
what is relative bioavailability
comparison of the bioavailability between formulations of a drug given either by the same or different routes of administration
can then choose the drug with the highest bioavailability
what is bioequivalence?
formulations containing the same dose of same chemical entity, generally in the same dosage form, intended to be interchangeable
Comparing formulations that have the same dose (and dosage forms) and see if they are equivalent and can be used interchangeably
how can we see differences in bioequivalence?
looking at the concentration time profile
if 2 bioequivalent drugs have a similar plasma concentration time profile what does this mean?
less likely to cause clinically relevant differences in therapeutic and adverse effects
rate limiting steps for oral absorption?
Disintegration time and dissolution rate Gastric emptying and intestinal transit Movement through membranes o Perfusion o Permeability limitations First-pass metabolism in the gut/liver
factors affecting intestinal absorption?
surface area
blood flow
permeability
why does gastric emptying control
emptying controls the delivery of drug to small intestine and affects the rate of absorption [Some of the drug can be absorbed in the stomach but that is a minor contributor]
factors affecting gastric emptying
age
coadministration with another drug
food
effect of anticholinergic drugs on gastric emptying
anticholinergic react the smooth muscles in the stomach, so gastric emptying is delayed
if you give a drug on a fasted stomach the transit time is….
very short so will be quickly delivered to the SI
fast delivery to the upper SI
does food effect small intestine transit time?
no not really
does particle size make a difference in the SI
no difference between particle sizes in the SI
enteric coated should be given on a what stomach? why?
FASTED
so they reach the SI as fast as possible to avoid the possibility that the EC will be damaged by sitting in the stomach [omeprazole, erythromycin]
poorly soluble drugs should be given on a what stomach? why?
FED
food deliberately delaying gastric emptying which will increase the time for dissolution of the molecule allowing more time for the molecule to be absorbed
risks associated with raised BMI
↑ Cardiovascular disease
↑ Diabetes
↑ Muscoskeletal disorders
↑ Some forms of cancer
what is gastric bypass
reduction in surface area of stomach, pH changes. Connected to distal region of the small intestine
does gastric bypass change pH
yes
how is drug absorption affected with gastric bypass?
Bypass of main areas of drug absorption – e.g., duodenum and the jejunum (~75cm bypassed) as the new stomach is connected to the further region of the SI
how does coeliac disease effect drug absorption?
Expression of intestinal CYP3A reduced on average to 15% of expression levels in healthy subjects
does coeliac disease effect first pass and bioavailability
yes
how does liver cirrhosis effect drug absorption?
intestinal enzymes may be affected
effect of liver cirrhosis on F and first pass?
reduced F
Reduced activity of many metabolic enzymes, extent depends on severity of disease
effect of chronic kidney disease on stomach?
increased gastric emptying time
increased pH
chronic kidney disease effects on metabolism and elimination
reduced renal elimination
expression of CYP450 enzymes changed for metabolism
