Oral PK lecture Flashcards
Advantages of oral administration
ease of administration
Disadvantages of oral administration
source of variability in exposure/response
takes time for drug to enter system circulation
some drug may be lost during absorption process
Immediate release products
Solids: tablets and capsules
most common
Modified release products
extended release
controlled release: approximates zero order release
sustained release: maintains drug release but not at constant rate
delayed release: enteric-coated aspirin
Phases of drug conc. vs. time profile
1st order absorption rate constant
Lag-time of absorption -tlag
extent of absorption- F
One compartment model
dA/dt=-K x A
K= first order
A= amount in body changes with time
Changing absorption kinetics
Ka decreases
- delays tpeak and decrease Cmax
-bioavailability of CL are unchanged
- AUC’s are identical
When Ka < Kel, absorption rate limits elimination
- decline of drug in plasma reflects absorption rather than elimination
- Flip flop kinetics
Lag time of absorption
absorption of drug after a single oral dose may not start immediately
The lag time can be anywhere from a few minutes to many hours
Complexities that alter lag time
Disintegration/dissolution
GI motility
Blood flow
Drug transport
Fraction of drug absorbed
portion of dose administered that reaches systemic circulation
F=1
Extravascular route: F can range from 0 to 1
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 AI or active moiety is absorbed from a drug product and becomes available at the site of action
Bioequivalance
bioequivalence is part of the approval process for generic drugs
Cmax, tpeak, and F are the primary PK parameters assessed for bioequivalence
Relative bioavailability
Fdrug A/Fdrug B
Compare AUC’s Drug B/Drug A
