Bioequivalence (2) [Uncomplicated Drugs] Flashcards
For Average BE studies, what is the minimum percentage difference b/w the test and reference drugs?
+/- 20%
For Average BE studies, what’s the sig. level?
0.05
For Average BE studies, what’s the power of the test set to?
0.8 (prob of detecting a diff if it truly exists b/w Test and Ref drugs)
For Average BE studies, what’s the typical sample size range?
24-36
For Average BE studies, do we typically use healthy or sick volunteers?
Healthy
In PK-BE studies, how many t1/2’s do we sample for?
at least 3 half lives
In PK-BE studies, when do we want to take more frequent blood samples from pts?
Around Cmax
In PK-BE studies, when assessing our data, what important PK parameters do we want to calculate? (3)
AUC, Cmax, Tmax
For BE to be established, drugs must be equivalent wrt ___ and ____ of drug absorption
rate, extent
What does Cmax represent?
peak exposure
What does AUC represent?
total exposure
In the past, how was BE established?
Mean AUC or Cmax of test drug was within +/- 20% of that of reference drug
What approach is used today to determine BE?
Confidence Interval approach
What is the ratio of means of the T and R drugs in a 90% confidence interval?
0.80-1.20
What is the ratio of means of the T and R drugs in a 90% confidence interval when the data are log transformed?
0.80-1.25
Why Log transform BE metrics (AUC, Cmax, Cp vs t)?
It makes the data normally distributed
T or F: Most PK parameters yield normal distributions
F
Mostly skewed dists
3 approaches to BE comparisons?
- Average BE
- Population BE
- Individual BE
T or F: Individual BE is the simplest approach to BE comparisons.
F
Average BE is the simplest approach
What’re the two types of study design?
- Crossover
2. Parallel
When is a parallel group design utilized?
When…
- drug causes physiological change that persists to the next treatment arm
- drug has long t1/2
- drug shows flip-flop kinetics
Does crossover or parallel study design allow examination of intrasubject variation?
Crossover
Which study design is preferred - crossover or parallel?
Crossover
Most common single oral dose design?
2-product, 2-period, 2-sequence, crossover
The Cmax value is used to evaluate ___ of absorption
rate
The AUC value is used to evaluate ___ of absorption
extent
When is BE of uncomplicated drugs concluded via the confidence interval approach?
When the 90% confidence intervals of both Cmax’s and AUC’s geometric mean ratios of the two fmlations fall within the BE range of 80-125%.
Which is worse: 90% Confidence Interval failing for AUC or Cmax?
AUC
Are t tests one sided or two sided for BE studies?
One-sided w/ 95% Confidence
