bioequivalence concepts

what are the two types of bioavailability?

relative and absolute

biovavailability is

rate and extend of absorption

what is the equation of ABSOLUTE bioavailability (F)

(AUC oral x Dose iv ) / AUC iv x Dose oral)

what is the equation of RELATIVE bioavailability (Frel)

F= AUCa / AUCb

active materials that produces desired pharmacological response or the material that is CONVERTED in the body (_______ or ______) to the pharmacologically active material

active ingredient, moiety, therapeutic moiety

used in manufacturing of the drug product and refers to the active ingredients to be used in the manufacturing drug product

active pharmaceutical ingredient

formulated drug that is prepared or manufactore or administration in humans (tablets, capsules, solutions for IV, inhalers, ointments)

drug product

(tablets, capsules, solutions for IV, inhalers, ointments are examples of

drug products

an inactive substance that serves as the vehicle or medium for a drug or other active substance, coatings, stabilizers, fillers, bindings, flavorings, diluents

excipients

do pharmaceutical equivalents HAVE to have the same expiration time?

NO

must have same

• dosage form

• strength

• active ingredient

do pharmaceutical equivalents HAVE to have the same shape?

NO they must have the same active ingredient and strength but they can have different excipients making them different shapes and colors

Do therapeutically equivalent drugs have to be bioequivalent?

YES

Thereapeuticallay equivalent drugs must be _______ ________ AND _______ _________

pharmaceutically equivalent AND bioequivalent

what is the purpose of the orange book?

show which drugs are interchangeable (therapeutically equivalent)

is the liquid version of Tylenol pharmaceutically equivalent to the tablet of the same strength?

NO must have same dosage from

they can be pharmaceutically alternatives

the FDA recommends use of a

_____ period

_______ sequence

_____ treatment

______- dose

CROSS OVER STUDY design

2

2

2

single

how to determine between PK studies, PD studies, comparative clinical trials, or in vitro studies when finding bioavailability

based on

• site of action

• ability of the study design to compare drug delivered to that site by the two products

what are the three different methods of PK Studies?

1. 2 period, 2 sequence, 2 treatment, single dose crossover

2. parallel

3. replicate study

how does the 2 sequence 2 period 2 treatment single dose cross over study work?

WHEN do you use this method over parallel method?

treatment A wait for washout treatment B and calculate bioavailability and PK parameters

treatment B wait for washout and then take treatment A THEN calculate bioavailability and PK parameters

if they are EQUIVALENT then you should have the same PK parameters no matter which comes first

if the half life is short you can calculate washout fairly easy use parraell if washout would take too long

if there are differences after the sequence takes place higher than 20% they are NOT equivalent

what PK parameters are you calculating for after each washout?

• area under curve (0—> t)

• area under curve extrapolated (last C/k)

• extent of absorption

• Cmax for rate of absorption

Bioavailability is determined by rate and extent which correspond to

extend = AUC

rate = Cmax

once you calculate the mean AUC and Cmax from your study participants of Drugs A and B how can you tell if they are bioequivalent?

AUC of drug A / AUC of drug B

OR

Cmax of drug A / Cmax of drug B

if the ratio is between 0..8- 1.25 or 80%-125% then the two drugs are bioequivalent

what information does the orange book give you

approved drug products with therapeutic equivalent calculations

in order for a drug to be considered _________ equivalent it must be _______ and ______ equivalent

therapeutically

pharmaceutically equivalent + bioequivalent (same rate and extent)

which codes are considered to be therapeutically equivalent to other pharmaceutically equivalent drugs?

A

which codes are considered to be therapeutically equivalent to other pharmaceutically equivalent drugs?

B