PK7 Bioequivaence Flashcards
What is the definition of bioavailability?
Bioavailability is the rate and extent to which a drug is absorbed from its formulation and becomes available at the site of action.
What factors influence bioavailability?
Drug formulation, administration route, physicochemical properties, metabolism, distribution, and elimination.
How is bioavailability (F) calculated?
F = (Quantity of unchanged drug reaching systemic circulation / Quantity of administered drug) * 100.
What is the bioavailability of intravenous (IV) administration?
100% (F = 1) because the entire dose reaches systemic circulation.
What is first-pass metabolism?
The metabolism of a drug before it reaches systemic circulation, occurring in the liver and gut wall.
What is AUC, and why is it important?
Area Under the Curve (AUC) represents total drug exposure over time and is used to assess bioavailability.
How is absolute bioavailability calculated?
F = (AUC_oral / AUC_IV) * (Dose_IV / Dose_oral) * 100.
What is the significance of absolute bioavailability?
It compares the bioavailability of a drug given via an extravascular route to its IV administration.
What is relative bioavailability?
The comparison of bioavailability between two different formulations of the same drug.
How is relative bioavailability calculated?
F_rel = (AUC_test / AUC_standard) * (Dose_standard / Dose_test) * 100.
Why is relative bioavailability important?
It assesses formulation differences, e.g., comparing a new oral tablet with an existing oral solution.
What does bioequivalence mean?
Two drug products have no significant difference in rate and extent of absorption when given at the same molar dose under similar conditions.
What parameters are used to assess bioequivalence?
AUC, C_max (maximum concentration), and T_max (time to reach maximum concentration).
What is the acceptable range for bioequivalence studies?
AUC and C_max must be between 80%-125% of the reference product.
Why are bioequivalence studies required for generic drugs?
To ensure they have the same efficacy and safety profile as the branded drug.
How do formulation changes impact bioavailability?
Variations in excipients, particle size, or manufacturing can alter drug absorption and lead to toxicity or reduced efficacy.
How does route of administration affect bioavailability?
IV > IM/SC/TD > Rectal > Oral > Topical (PROT mnemonic: Parenteral > Rectal > Oral > Topical).
What is the salt factor (S), and why is it important?
The fraction of the free drug present in a salt or ester form, impacting dosing calculations.
How is the salt factor used in dose calculations?
Dose_salt = Dose_free / S.
How does first-pass metabolism impact oral bioavailability?
It reduces bioavailability as the drug is metabolized before reaching systemic circulation.
What are examples of drugs with significant first-pass metabolism?
Propranolol, morphine, and nitroglycerin.
What factors impact oral drug absorption?
Gastric pH, gastric emptying, enzymatic degradation, and interactions with food or other drugs.
Why do modified-release formulations require separate bioavailability studies?
Their altered drug release profiles can significantly affect absorption and systemic exposure.
What is the difference between an innovator drug and a generic drug?
The innovator drug is the original patented product; generics must demonstrate bioequivalence but may differ in excipients and manufacturing sites.
What is the significance of C_max and T_max in bioavailability studies?
C_max represents peak drug concentration; T_max indicates the time taken to reach peak concentration, both affecting drug efficacy and safety.
