Lecture 5: Bioequivalence testing of oral medicines II Flashcards Preview

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Flashcards in Lecture 5: Bioequivalence testing of oral medicines II Deck (33)
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1
Q

What are the data requirements for a bioequivalence report?

A
  • name & signature of responsible investigators
  • name & B/N of the products compared
  • period of dates
  • site of study
  • details & results of assays & other tests
  • deatails of how PK parameters were determined
  • full protocol for the study (incl. written consent form)
  • evidence that study protocol was approved by an appropriate ethics committee etc.
2
Q

What sort of data is required for evidence of a BE study?

A

comparative bioavailability data. The blood plasam or serum concentration-time curve provides the best measure of bioavailability for medicines with a systemic effect

3
Q

What is the bioavailability factor?

A

the ratio between total AUC of the test product and total AUC of the reference product.

4
Q

What is F?

A

the fraction of an administered dose that actually reaches systemic circulation

5
Q

What does an F value of 0 mean?

A

no drug absorption

6
Q

What does an F value of 1 mean?

A

complete drug absorption

7
Q

What is absolute bioavailability?

A

when an IV bolus injection is used as a reference.

This is because the entire administered dose is introduced directly to the systemic circulation. There are no absorption barriers to cross and is therefore considered totally bioavailable

8
Q

What is relative bioavailability?

A

the availability of a drug product as compared to similar dosage form of the SAME drug given in the SAME dose

9
Q

What does relative bioavailability determine?

A

formulation differences on drug absorption

10
Q

How is relative bioavailability obtained?

A

by comparing the AUC of the test and reference product.

11
Q

What is the criteria used for bioequivalence of relative bioavailability?

A

the ratio of the AUCs should be within 0.8-1.25

12
Q

Why are single dose studies preferred?

A

they can be completed in a shorter period of time

They involve less exposure of volunteer subjects to the drug

13
Q

Why are multiple dose or steady state studies used?

A
  • When analytical methods are not sensitive enough after a single dose
  • when studying controlled release products
  • when studying a drug which is too toxic
14
Q

What is ka and ke?

A
ka = rate of absorption
ke = rate of elimination
15
Q

What would a curve look like if Ka> Ke?

A

Left skewed with peak near the start of time.

16
Q

How is a maximum point of drug content in the plasma reached?

A

Initially, as the drug is administered and plasma concentration increases, the rate of elimination will increase while the rate of absorption decreases. This is due to the concentration in the GIT decreasing (thus reducing the diffusion drive into cells)

The two rates will balance at a point which is the maximum plasma concentration.

17
Q

What happens at the start of a Ka>ke curve?

A

the rate for absorption is high because the concentration in the GIT is high.
The rate for elimination is low because the concentration in the plasma is low so there is an observable overall increase in plasma concentration

18
Q

What happens near the end of a ka>ke curve?

A

the rate of absorption nears 0 when the concentration in the GIT nears 0. Only elimination occurs and the rate of elimination is dependent on the existing plasma concentration

19
Q

What kinds of drugs would have ke>ka?

A

drugs with short biological half lives
drugs that exhibit prolonged absorption
drugs with a combination of the above

20
Q

What is onset?

A

the time required to achieve the minimum effective plasma concentration following administration of the dosage form

21
Q

What is duration?

A

the period during which the concentration of drug in plasma exceeds the minimum effective concentration

22
Q

What sort of kinetics does a single IV bolus dose follow?

A

first order kinetics, where if the data is plotted as a log of plasma conc. vs. time a straight line is formed.

23
Q

What are the characteristics of first order kinetics?

A

log plasma conc gives straight line
known as first order elimination
the drug concentration changes with respect to time as a function of the drug concentration remaining, and a first order rate constant .

rate = -kC where the negative indicates a decreasing tendency (as in the case of elimination)

24
Q

What is the elimination rate constant?

A

Concenration over a period of time = initial concentration x e^-kt

This is the fall in plasma drug concentration after a single dose

25
Q

What is half life?

A

the time taken for the amount of drug in the body (or plasma conc) to fall by a half.

k = 0.693/ t1/2

26
Q

How is half life related to elimination rate constant?

A

half life is a reciprocal function of the elimination rate constant

27
Q

What is Kel?

A

the terminal elimination rate constant or elimination half life

28
Q

what are some other PK parameters that may be explored in a BE study?

A

total urinary excretion

29
Q

What is an old method of calculating the area under the curve?

A

divide the area into triangles and trapeziums. calculate each individual area and add them together

30
Q

What is the area of a trapezium?

A

area = h(a+b)/2

31
Q

What is the area of a triangle?

A

area = (axb)/2

32
Q

How should the data be reported?

A

Two graphs to be drawn for each subject.
Two graphs to be drawn for the mean values of all subjects

Of these graphs, one should be linear and the other should be semi-logarithmic of the concentrations from the reference and test formulations against sampling times

33
Q

What is a semi logarithmic plot?

A

where plasma concentration axis is log-ed