Bioequivalence (1) Flashcards
This model predicts oral absorption based on dissolution
Biopharmaceutics Classification System
How does the American FDA’s def’n of BIOAVAILABILITY differ from that of Canada’s TPD (Therapeutic Products Directorate) def’n?
FDA doesn’t directly state that it relates to the drug’s plasma concentration.
TPD’s def’n implies that bioavailability of a drug is directly related to its conc in the blood (Cp)
T or F: Generics drive healthcare costs up.
F
Down
T or F: Following the “Hatch-Waxman Act”, generics had to prove efficacy of their products.
F
Efficacy was proven by the inventor company. All that generic companies had to prove was bioequivalence between their drug and and brand name drug.
What was thalidomide used to treat?
Morning sickness in pregnant women.
F =
[AUC(oral)/AUC(IV)][Dose(IV)/Dose oral]
Absolute bioavailability
In single dose evaluation of bioavailability, what parameters characterize rate and extent of bioavailability?
AUC(0-∞), Cmax, and tmax
What is considered highly soluble under the Biopharmaceutics Classification System?
Soluble in < or = 250 mL aqueous media over pH 1.2-6.8 @ 37ºC
This model correlates in vitro dissolution w/ in vivo BA
Biopharmaceutics Classification System
Do generics have the same API as the innovator drug?
Yes
What aspect of their drugs did generic companies have to prove after the Hatch-Waxman Act?
Pharmaceutical equivalence and BE (bioequivalence)
What aspect of BA is described by AUC?
EXTENT of absorption
What fraction needs to be absorbed in order to be considered to have good permeability (according to the Biopharmaceutics Classification System)?
> or = 80%
What is considered rapid dissolution under the Biopharmaceutics Classification System?
> 85% of drug dissolves within 30 mins using USP Apparatus I or II
In in vitro studies, drugs are classified according to what 3 criteria in the Biopharmaceutics Classification System?
- Aqueous solubility
- Dissolution rate
- Intestinal permeability
How many solubility-permeability drug classes are there in the Biopharmaceutics Classification System?
4
According to the Biopharmaceutics Classification System, two drugs will have the same rate and extent of absorption when… (2)
- they have the same C vs. t profile at intestinal membrane surface
- they have the same in vivo dissolution profile under all luminal conditions
Can we say that two drugs are BE based on AUC data only?
NO, b/c while the extent of absorption may be equivalent, we know nothing about the rate of absorption
What are generic drugs?
Copies of brand-name drugs
T or F: Generics drive healthcare costs down.
T
They are exact versions of the innovator product (made with same ingredients from same factory). They only differ in packaging
Pseudo-generics
What did the “Hatch-Waxman Act” establish?
ANDA (abbreviated new drug application procedure)
When can we waive BE studies? (5)
- Soln intended for IV use
- Topical drug
- Oral drug not meant to be absorbed
- Inhaled drug
- Drug contains no excipient known to affect BA
In multiple dose evaluation of bioavailability, what parameters characterize rate and extent of bioavailability?
AUC(τn-τn+1) and % fluctuation
Are generics intended for the same therapeutic use as the innovator drug?
Yes
The extent of absorption is limited by permeability for drugs of this permeability-solubility class.
III
T or F: B/w 1962 and 1984, there was a boom in generic drug production.
F
It was too expensive due to the Federal Food, Drug, and Cosmetic Act amendment in 1962
This solubility-permeability drug class has a low aqueous solubility and high permeability
II
What aspect of BA is described by Cmax and tmax?
RATE of absorption
Most diffs in product performance b/w generics and brand names is reflected in what?
Dissimilar Cp vs. t
Name 2 diffs b/w generics and brand name drugs.
Generics…
- look different
- are cheaper
Name the 4 types of bioequivalence studies in order of preference by FDA/TPD.
- PK-BE (pharmacokinetic)
- PD-BE (pharmacodynamic)
- Comparative Clinical Study
- In Vitro study
The extent of absorption is limited by dissolution rate for drugs of this permeability-solubility class.
II
The extent of absorption is very poor for drugs of this permeability-solubility class.
IV
This solubility-permeability drug class has a low aqueous solubility and low permeability
IV
A biowaiver is readily gained for this permeability-solubility drug class.
I
Why are two bioequivalent drugs considered interchangeable?
Because they’re assumed to be therapeutically equivalent
What is the slowest step in absorption?
Dissolution
What is considered highly permeable under the Biopharmaceutics Classification System?
Absorption is >90% of administered dose
Why did generic companies stop developing generics after 1962?
Because they were req’d to prove safety, efficacy, and BE in their drugs (before 1962, only safety had to be proven)
In 1984, the “Drug Price Competition and Patent Term Restoration Act” was brought into existence. What’s another name for this act?
the “Hatch-Waxman Act”
Define “Pharmaceutical Equivalents”
Two drugs that…
a. have identical APIs in identical amts in comparable dosage forms
b. have diff excipients
In the Biopharmaceutics Classification System, what drug is considered the standard for good permeability?
Metoprolol
How is the American FDA’s def’n of BIOAVAILABILITY similar to that of Canada’s TPD (Therapeutic Products Directorate) def’n?
They both consider the rate and extent of absorption of drug.
Are pseudo-generics more expensive than actual generics?
Yes.
This solubility-permeability drug class has a high aqueous solubility and low permeability
III
Do PK-BE studies use the highest or lowest dose approved for the innovator (R; reference) drug?
Highest
When can we say that two drugs (test and reference drug) are bioequivalent?
When the rate and extent of absorption profiles for both drugs (that contain the same drug) are similar or the same.
What two parameters does bioequivalence consider?
- Rate of absorption
2. Extent of absorption
The extent of absorption is very good for drugs of this permeability-solubility class.
I
This solubility-permeability drug class has a high aqueous solubility and high permeability
Class I
Two broad classifications for factors that affect BA (F) and BE?
- Factors that affect drug dissolution or release from dosage form
- Factors related to excipients that affect drug stability, absorption and metabolism
In what ways (2) are BAs of a drug from two fmlations compared?
- Cp vs t profiles
2. AUC, Cmax, and tmax
What is relative bioavailability?
Extent and rate of BA of drug from two or more diff dosage forms given by the same route of administration
Where does most absorption take place?
Small intestine
