Bioavailability

Question 1

Generic drugs are ____ and ____ alternatives to brand name prescriptions

Answer 1

safe and effective

Question 2

T/F One of the primary ways physicians can practice cost effective prescribing is by offering patients a generic medicine when one is available

Answer 2

TRUE

Question 3

When can a generic be created?

Answer 3

once the patent expires on the innovator

Question 4

What are the applications of bioavailability and bioequivalence studies? (5)

Answer 4

• determine the effect of various formulations
• determine food effects
• evaluate the effect of age, disease, etc
• assess route of administration effect or first pass effect
• ANDA

Question 5

ANDA

Answer 5

abbreviated new drug application–> used for the approval of generic drugs

Question 6

The goal of bioavailability studies is to….

Answer 6

control all the variables except for the one you are testing

Question 7

bioequivalent= similar

Answer 7

bioavailability

Question 8

Steps for bioavailability study? (5)

Answer 8

1. recruit healthy volunteers
2. administer the drugs to volunteers
3. Collect samples of biological fluids (typically blood)
4. Analyze
5. Draw graph

Question 9

availability

Answer 9

• measure of relative amount absorbed (looking at ratios of AUC)
• range from 0 to 1

Question 10

______ compares AUC to an IV DOSE

Answer 10

absolute availability

Question 11

_______ compares AUC to a reference

Answer 11

relative availability

Question 12

Which availability is used for ANDA?

Answer 12

relative

Question 13

How can you calculate the total amount absorbed?

Answer 13

absolute availability

Question 14

A test oral formulation has the same area under the plasma concentration-time curve as the reference formulation. This means that the two formulations…
A) are bioequivalent by definition- related to AUC
B) deliver the same total amount of drug to the body but are not necessarily bioequivalent
C) are bioequivalent if they both meet USP dissolution standards
D) deliver the same total amount of drug to the body and are, therefore, bioequivalent
E) have the same rate of absorption

Answer 14

B) deliver the same total amount of drug to the body but are not necessarily bioequivalent because the rate may be different (if the rate is dif. Then they may not be considered bioequivalent)

Question 15

excretion vs. metabolism

Answer 15

excretion: drug is unchanged
metabolism: drug is converted to some other form

Question 16

urinary excretion studies

Answer 16

graph the cumulative excretion

Question 17

T/F Urinary Excretion studies increase and then decrease.

Answer 17

FALSE: starts at zero–> increases until it plates–> It NEVER decreases because it is cumulative

Question 18

When a cumulative excretion graph plateaus, what does this mean?

Answer 18

all the drug is out of the body; time to plateau is related to the rate of absorption

Question 19

Potassium Penicillin G was given IV to volunteers, 80% of a 500mg dose was recovered unchanged in the urine. 280 mg was recovered in urine when the same dose was given IM to the same subjects. Calculate the availability of the IM injection. What type of availability is this?

Answer 19

F = 280/400 = 0.70; absolute

Question 20

urinary excretion studies are used for.. (2)

Answer 20

• drugs extensively eliminated in the urine

- drug where UT is site of action

Question 21

For valid estimates in the urinary excretion studies… (3)

Answer 21

• excretion to extent of greater than 25%
• analysis must be specific for unchanged drug
• complete urine collection

Question 22

_____ the study design usually used for bioavailability/ bioequivalence testing

Answer 22

crossover design (typically single dose study)

Question 23

Crossover designs have a period known as wash out period…what does this mean?

Answer 23

allows time for all the drug from the first round to be completely out of the system before administering the next

Question 24

______ proof of bioequivalence is required for generic products

Answer 24

reference product

Question 25

the reference is the _____ product. What does the reference product have to have?

Answer 25

innovator: NDA (new dug application) have to show efficacy and safety

Question 26

Bioequivalence criteria?

Answer 26

you want EVERYTHING to be the same--> to show that the PRODUCT is the reason for any differences in the outcome

Question 27

______ or ____ are used for bioequivalence testing

Answer 27

90% confidence interval or two, one sided t-test

Question 28

90% confidence interval or two, one sided t test: - Bioequivalent if entire range is between _____ and _____ - testing the ____ - Need to be ____ close to each other

Answer 28

- 0.80 and 1.25 - AUC - 20%

Question 29

Cmax and Tmax are used for the bioequivalence, but....

Answer 29

they are not as strict

Question 30

Who completes the bioequivalent studies?

Answer 30

the company trying to get it on the market

Question 31

Approved Drug Products with Therapeutic Equivalence Evaluations=

Answer 31

Orange Book

Question 32

____ code are therapeutically equivalent

Answer 32

A

Question 33

Therapeutically equivalent =

Answer 33

bioequivalent (similar rate and extent of absorption)

Question 34

T/F Therapeutic effect is tested in the Orange Book

Answer 34

FALSE: NOT

Question 35

RLD abbreviation?

Answer 35

reference listed drug

Question 36

B codes

Answer 36

NOT therapeutically equivalent

Question 37

______ is the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action

Answer 37

bioavailability

Question 38

For drug products that ARE not intended to be absorbed in to the blood stream bioavailability.....

Answer 38

may be assessed by measurements intended to reflect rate and extent

Question 39

____ is the absence of a significant difference in the rate at which or extent to which the active ingredient is pharmaceutical equivalent or alternative becomes

Answer 39

bioequivalence

Question 40

T/F A product may also be considered bioequivalent to an innovator product if the difference in rate of absorption of the drug between the two products is intentional

Answer 40

TRUE

Question 41

_____ a finished dosage form that contains an active ingredient

Answer 41

drug product

Question 42

narrow therapeutic index.: there is less than ____ difference in median lethal dose and median effective dose values for a drug product

Answer 42

2-fold

Question 43

To safely and effectively use drug products with narrow therapeutic index require (2)

Answer 43

- careful dosage titration | - patient monitoring

Question 44

______ drug products that contain the SAME active ingredient, are of the same dosage form, route of administration and are identical in strength

Answer 44

pharmaceutical equivalents

Question 45

T/F pharmaceutical equivalents are NOT allowed to differ in shape, scoring configuration, excipients, release mechanism

Answer 45

FALSE: are (they can not differ in strength, quality, purity and identity)

Question 46

________ drug products contain the same THERAPEUTIC MOIETY, but different SALTS, ESTERS, or complexes of that moiety

Answer 46

pharmaceutical alternatives

Question 47

T/F Different dosage forms and strengths within a product line by a single manufacturer are thus pharmaceutical alternatives

Answer 47

TRUE

Question 48

Therapeutic equivalents are expected to have the same ____ and ______ when administered to patients under the conditions specified in the labeling

Answer 48

clinical effect and safety profile