L46 - Extrvascular Administration 2 Flashcards
Why is k difficult to estimate from the abs phase? Why can it be estimated from the elim phase?
- Both absorption and elimination occur
- after tmax, drug available at absorption site is finished
What does eqn1 simplify to at the lim phase?
Cterminal = B x e^-kt
How to estimate k from the elim phase?
- from the slope
- extrapolate to t=0, provides B
- use lnCterminal = lnB - kt
What is the AUC of the plasma conc vs time profile following an exravascular administration?
AUC = DxF / Cl
D - dose
F - fraction absorbed
Cl - clearance
What can vol of distribution not be directly obtained from?
Oral data
When can you estimate V from extravascular data?
have Cl and k, Cl = kxV
What do you look at to get tmac/time of peak plasma conc?
- time reequired for Cmax
- indication of rate of drug abs from dif formulations
- tmax shorter for faster abs, less time to required to reach Cmax
What do you look at to get Cmax / peak plasma drug conc?
- max plasma drug conc after extravascular admin
- is Cmax enough for therapeutic response?
- is Cmax too high? Toxic?
What is bioavailability?
- Relative amount of an administered dose that reaches systemic circulation and rate at which this occurs
- the rate and extent to which the API or therapeutic moiety is absorbed from a product and becomes available at the site of drug action
When are MPs are pharmaceutically equivalent?
If they contain the same amount of the same active substance in the same dosage forms that meet the same or comparable standards
What does pharmaceutical equivalance not imply?
- Bioequivalance
- as differences in excipients and/or manufacturing process can lead to faster/slower dissolution and/or absorption
What are pharmaceutical alternatives?
MPs with different salts, esters, ethers, isomers, mixtures of isomers, complexes/derivatives of an active moiety, which differ in dosage form or strength
What are therapeutically equivalent products?
Products that can be substituted, will produce same clinical effect, safety profile as prescribed product
(Pharmaceutical equivalents and bioequivalent)
What is the EMA definition of bioequivalence?
If 2 MPs containing same API are pharmaceutically equivalent/alternatives and their bioavailability after admin in same molar dose are within limits
What is the US FDA definition for equivalence?
Absence of a sig dif in rate and extent to which API in pharmaceutical equivalents/alternatives become available at site of drug action when administeres at same molar dose under similar conditions
What are generic products (EMA)?
Medicine developed to be the same as reference medicine already authorised
What are generic products like (EMA)?
- contains same active substance as RM, same dose, treat same disease, same pharmaceutical form
- same quantity of API
What is generic drug development like?
- product should be pharmaceutically equivalent to reference listed drug (RLD)
- bioequivalent to RLD
- therapeutically equivalent
What do you need to compare from the test and reference formulations?
- extent of absorption - reltaive bioavailability (look at eq on ppt)
- rate of absorption
What is the criteria for BE regulatory comparisons?
- when 90% confidence interval of ratio of log transformed exposure meausre falls entirely within 80-125%
- dif in clinical exposure <= 20%
