Bioavailability Flashcards
Generic drugs are ____ and ____ alternatives to brand name prescriptions
safe and effective
T/F One of the primary ways physicians can practice cost effective prescribing is by offering patients a generic medicine when one is available
TRUE
When can a generic be created?
once the patent expires on the innovator
What are the applications of bioavailability and bioequivalence studies? (5)
- 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
ANDA
abbreviated new drug application–> used for the approval of generic drugs
The goal of bioavailability studies is to….
control all the variables except for the one you are testing
bioequivalent= similar
bioavailability
Steps for bioavailability study? (5)
- recruit healthy volunteers
- administer the drugs to volunteers
- Collect samples of biological fluids (typically blood)
- Analyze
- Draw graph
availability
- measure of relative amount absorbed (looking at ratios of AUC)
- range from 0 to 1
______ compares AUC to an IV DOSE
absolute availability
_______ compares AUC to a reference
relative availability
Which availability is used for ANDA?
relative
How can you calculate the total amount absorbed?
absolute availability
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
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)
excretion vs. metabolism
excretion: drug is unchanged
metabolism: drug is converted to some other form
urinary excretion studies
graph the cumulative excretion
T/F Urinary Excretion studies increase and then decrease.
FALSE: starts at zero–> increases until it plates–> It NEVER decreases because it is cumulative
When a cumulative excretion graph plateaus, what does this mean?
all the drug is out of the body; time to plateau is related to the rate of absorption
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?
F = 280/400 = 0.70; absolute
urinary excretion studies are used for.. (2)
- drugs extensively eliminated in the urine
- drug where UT is site of action
For valid estimates in the urinary excretion studies… (3)
- excretion to extent of greater than 25%
- analysis must be specific for unchanged drug
- complete urine collection
_____ the study design usually used for bioavailability/ bioequivalence testing
crossover design (typically single dose study)
Crossover designs have a period known as wash out period…what does this mean?
allows time for all the drug from the first round to be completely out of the system before administering the next
______ proof of bioequivalence is required for generic products
reference product
the reference is the _____ product. What does the reference product have to have?
innovator: NDA (new dug application) have to show efficacy and safety
Bioequivalence criteria?
you want EVERYTHING to be the same–> to show that the PRODUCT is the reason for any differences in the outcome
______ or ____ are used for bioequivalence testing
90% confidence interval or two, one sided t-test
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
- 0.80 and 1.25
- AUC
- 20%
Cmax and Tmax are used for the bioequivalence, but….
they are not as strict
Who completes the bioequivalent studies?
the company trying to get it on the market
Approved Drug Products with Therapeutic Equivalence Evaluations=
Orange Book
____ code are therapeutically equivalent
A
Therapeutically equivalent =
bioequivalent (similar rate and extent of absorption)
T/F Therapeutic effect is tested in the Orange Book
FALSE: NOT
RLD abbreviation?
reference listed drug
B codes
NOT therapeutically equivalent
______ 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
bioavailability
For drug products that ARE not intended to be absorbed in to the blood stream bioavailability…..
may be assessed by measurements intended to reflect rate and extent
____ 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
bioequivalence
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
TRUE
_____ a finished dosage form that contains an active ingredient
drug product
narrow therapeutic index.: there is less than ____ difference in median lethal dose and median effective dose values for a drug product
2-fold
To safely and effectively use drug products with narrow therapeutic index require (2)
- careful dosage titration
- patient monitoring
______ drug products that contain the SAME active ingredient, are of the same dosage form, route of administration and are identical in strength
pharmaceutical equivalents
T/F pharmaceutical equivalents are NOT allowed to differ in shape, scoring configuration, excipients, release mechanism
FALSE: are (they can not differ in strength, quality, purity and identity)
________ drug products contain the same THERAPEUTIC MOIETY, but different SALTS, ESTERS, or complexes of that moiety
pharmaceutical alternatives
T/F Different dosage forms and strengths within a product line by a single manufacturer are thus pharmaceutical alternatives
TRUE
Therapeutic equivalents are expected to have the same ____ and ______ when administered to patients under the conditions specified in the labeling
clinical effect and safety profile
