Bioavailability and Bioequivalence (Leonila Estole-Casanova, MD)

Question 1

Define: Bioavailability

Answer 1

Extent to which an active pharmaceutical agent is absorbed unchanged and becomes available in general circulation

Question 2

When are two substances bioequivalent?

Answer 2

1. Pharmaceutically equivalent or alternatives
2. Similar Cmax, Tmax and AUC after administration of same molar dose under same conditions
3. Essentially same effects

Question 3

What is an important assumption with bioavailability?

Answer 3

Amount of drug reaching plasma is the amount that reaches the target site

Question 4

What are the two types of bioavailability?

Answer 4

Absolute

Relative

Question 5

How is absolute bioavailability derived?

Answer 5

Comparison of AUCs of extravascular and IV administration

Question 6

T/F: If the drug is administered by IV, the F is 1.

Answer 6

True

Question 7

What is the formula for absolute bioavailability?

Answer 7

F = (AUCPo/DosePo)/(AUCIV/DoseIV)

Question 8

When is relative bioavailability used?

Answer 8

When there is no data from IV administration

1. Expensive IV preparation
2. Low solubility of drug
3. Contraindications of IV route

Question 9

What is the formula for relative bioavailability?

Answer 9

Relative Bioavailability = (AUCa)/(AUCb)

where AUCb is the reference standard exposure

Question 10

What are the factors affecting bioavailability with respect to absorption?

Answer 10

1. Variable absorption from GIT
2. Drug too hydrophilic (atenolol)
3. Grapefruit juice (inhibit reverse transporter)

Question 11

What drugs are degraded extensively by the first pass effect?

Answer 11

Lidocaine and propanolol

Question 12

T/F: Rate of absorption is measured by Tmax.

Answer 12

True

Question 13

What is the range of bioavailability for IM and SC routes?

Answer 13

75 - 100%

Question 14

What is the range of bioavailability for oral and inhalation routes?

Answer 14

5 - 100%

Question 15

Do rectal and transdermal routes provide less first pass effect? What are their bioavailability ranges?

Answer 15

Yes.

Rectal - 30 - 100%
Transdermal - 80 - 100%

Question 16

In bioequivalence, the (1) profiles of two formulations must be equal.

Answer 16

(1) plasma concentration vs. time

Question 17

What is the fundamental reason for performing bioequivalence testing?

Answer 17

To ensure the quality of generic drug products

Question 18

What is considered one of the most successful pieces of legislation passed?

Answer 18

Hatch-Waxman Amendments to FFD & C Act of 1984

Increased prescription of generics (from 12% - 44% in 16 years)

Question 19

How long are the innovator drug patents in effect?

Answer 19

Around 20 years

Question 20

If you are developing a generic or alternative drug, what do you have to prove?

Answer 20

Safety
Efficacy
Affordability

Question 21

What are the NDA requirements for branded drugs?

Answer 21

1. Chemistry
2. Manufacturing
3. Controls
4. Labeling
5. Testing
6. Animal Studies
7. Clinical Studies
8. Bioavailability

Question 22

What are the NDA requirements for generic drugs?

Answer 22

1. Chemistry
2. Manufacturing
3. Controls
4. Labeling
5. Testing
6. Bioequivalence

Question 23

What are the requirements for a generic drug?

Answer 23

1. Same active ingredients
2. Same route of administration
3. Same dosage form
4. Same strength
5. Same condition of use

Question 24

Define: Pharmaceutical Alternative

Answer 24

Same molar amount and active pharmaceutical moieties

Different dosage form and chemical form

Question 25

Give examples of pharmaceutical alternatives

Answer 25

Tetracycline phosphate and tetracycline hydrochloride | Metformin immediate and extended release tablets

Question 26

Define: Pharmaceutical Equivalence

Answer 26

Same molar amount, active pharmaceutical ingredients, dosage form and route e.g. diazepam 5 mg

Question 27

Can bioequivalent substances be either pharmaceutical alternatives or equivalents?

Answer 27

Yes

Question 28

Define: Therapeutic Equivalence

Answer 28

Pharmaceutical equivalents or alternatives administered in same molar dose, route and with same effects

Question 29

T/F: Therapeutically equivalent drugs must be bioequivalent.

Answer 29

False

Question 30

T/F: Pharmaceutical equivalence = therapeutic equivalence

Answer 30

False

Question 31

Pharmaceutical equivalence is acceptable in which dosage forms?

Answer 31

Aqueous solutions Powders for reconstitution Gases

Question 32

What factors contribute to the differences in drug performance in vivo?

Answer 32

1. Drug particle size 2. Excipients 3. Manufacturing equipment or process 4. Site of manufacture

Question 33

Are bioequivalent drugs therapeutically equivalent?

Answer 33

They should be.

Question 34

What is the battle cry of bioequivalence?

Answer 34

We want to be the same!

Question 35

What is the standard model of testing in bioequivalence trials?

Answer 35

2-treatment cross-over study There is a wash-out period.

Question 36

What parameter refers to the total amount of active drug that reaches the systemic circulation?

Answer 36

AUC 0 - t

Question 37

Cmax and Tmax assess the (1) of absorption, while AUC assesses the (2) of absorption.

Answer 37

(1) rate | (2) extent

Question 38

T/F: If Cmax and AUC are the same, CL, Vd, k, and half life won't be very different.

Answer 38

True

Question 39

What is the statistical requirement for bioequivalence?

Answer 39

AUC and Cmax must be in between 80 - 125% for a 90% confidence interval.

Question 40

Good manufacturing practices entails that the producers take proactive steps to ensure that their products are?

Answer 40

Safe, pure and effective