E1 L4: Oral Dosing Flashcards
3 routes of admin
IV bolus
Iv infusion
Extravascular
Peak concentration at CP0
Measure of drug in the veins
IV bolus
Drug accumulates in the body until it reaches a plateau
IV infusion
Outside of the vasculature
Anywhere outside of vein
oral absorption
Intransal, patch
Extravascular
Why extravascular graph looks different
All of the drug is going into GI tract but that is not where we measure - measure in blood - some is lost in transit
CMax points for IV bolus, IV infusion and Extravascular
IVB - C0
IV I - plateau
Ex: peak
Tmax points for IV bolus, IV infusion and Extravascular
IV B - 0
IV infusion - (where plateau ends
Ex: Where peak stops
AUC: bigger the area…
Greater exposure to drug over time
Advantage of oral drug admin
Ease of admin
Disadvantages of oral drug admin
Source/variability of response
Takes time for drug to enter systemic circulation following admin
Some drug may be lost during the absorption process
Two types of oral drug products
Immediate release and modified release
Immediate release products
tablets and capsules (most common)
Liquids: syrups, elixirs, suspensions, and emulsions
Modified release products:
ER:
controlled release - approximates zero order release
Constant drug release over time
Sustained-release: maintains drug release but not at a constant rate
Delayed Release:
common examples is enteric-coated aspirin
Oral drug formulations
Immediate release
Sustained release
Controlled release
Delayed release
If the same dose is given in three different formulations, will they all have the same AUC
yes
Comparison of oral admin with IV admin
Absorption delays the magnitude of the peak compared with that seen following an equal IV bolus dose
IV bolus is - order elimination
1st order
Iv infusion is - order elimination
0 order
Oral admin is - order of elimination
First order (amount in absorption compartment changes over time)
Absorption occurring faster than elimination =
Net concentration
Ka * Abs > kel * A
Absorption phase
Ka * Aabs = Kel * A
Cmax
Ka * Aabs < Kel *A
Post absorption phase
T/F: if Ka < kel, absorption rate limits elimination
True
Rate of absorption is controlling rate of elimination of drug
Only way to eliminate faster
Increase Ka (flip-flop kinetics)
tlag def
Absorption of a drug after a single oral dose may not start immediately - can be anywhere from minutes to hours
Complexities that alter tlag:
Disintegration/dissolution
GI motility
Blood flow
Drug transport
Why is cmax lower for oral dose?
Loss of drug during absoprtion
Fraction of drug absorbed (F)
Portion of dose administered that reaches systemic circulation
Factors that can affect F
Dissolution
Gut wall permeation
Active transport
Metabolism
Biliary excretion
FDA definition of bioavailability
“The rate and extent to which the active ingredient or active moiety is absorbed from a drug and becomes available at the site of action
F = Bioavailability
NO - NOT a measure of the rate of absorption (only extent)
Fraction of drug absorbed equation (absolute bioavailability)
F =(AUC oral)/(Dose oral)/ (AUC IV)/ (Dose IV)
