Fang PDFs Flashcards
What metric is used to define the rate of absorption?
Cmax
Comparing a drug product’s oral area under the curve (AUCo) to its own IV area under the curve (AUCiv) is an estimate of what?
Absolute Bioavailability
Comparing the Plasma Concentration vs. Time profile of a Test Product to its comparator Reference Product is an estimate of what?
Relative Bioavailability
What type of test volunteers should be used when conducting Comparative Bioavailability Studies?
Normal & Healthy Patients (as conclusions drawn from the study should hold true in populations).
How would we define ‘bioequivalence’?
Test Product is expected to have the same therapeutic effect & safety profile as its Reference Product.
What is a ‘Two Period Crossover’ study, and what benefit does it have over other study types?
-Same subject gets Test Product, then gets Reference Product at a different time.
-Intra-subject error is lower (in comparison to Inter-subject Error if we used more than one subject to compare the two products).
What is a ‘Replicated Crossover’ study? What pros & cons does it have compared to other study types?
-Each formulation (ie. Test & Reference Product) examined more than once in a patient.
-Less subjects required (good) but more patient appearances needed (bad).
What types of patients would it be suitable to conduct a ‘Crossover Without Washout’ type study?
For those whom abrupt drug discontinuation would be unethical or unsafe to do.
What types of drug products would it be advisable to conduct a ‘Parallel’ study type?
1) Long t1/2elim
2) Drug w depot effects
What four study factors influence how many subjects should be used?
1) Standard
2) Mean Difference (btw Test & Reference Formulations)
3) Intra-Subject Variance
4) Study Power
What is the bare minimum number of test subjects that should be used in Comparative Bioequivalency Studies?
12
In bioequivalence studies with more than twenty subjects, what percentage of patients can be excluded due to being considered “statistical outliers”?
No more than 5%
In bioequivalence studies with less than twenty subjects, what number of patients can be excluded due to being considered “statistical outliers”?
1
What two PK parameters are typically examined in the determination of statistical outliers?
AUC & Cmax
When conducting bioequivalence studies in the “Fasted State”, how long must subjects go without food? Water?
Food: 8hrs before drug administration (but no closer than that).
Water: Up to 1hr before drug administration.
In “Fasted” bioequivalence studies, after how many hours post-administration of drug are subjects okay to eat?
4hrs (so long as meals are standardized across patient groups).
How would water intake timelines differ in a “Fasted” study if the formulation of the product was an ODT (instead of a traditional IR oral tablet)?
IR: Water up to 1hr before drug admin, can drink water right after!
ODT: Water up to 1hr before drug admin, no water for 1hr after dose given!
