BA + BE Flashcards
Define bioavailability
The extent and rate at which a substance is delivered from a pharmaceutical form and becomes available in general circulation.
How is absolute bioavailability determined?
Use of IV admin is needed, where;
- comparison of F of a particular dosage form with its corresponding IV admin.
F = [AUC(ev)/AUC(iv)] x [Dose(iv)/dose(ev)]
How is relative bioavailability determined?
No IV reference is needed, where;
- Compare AUC values (ratio) of different dosage forms/formulation
- Determine effect of formulation differences on drug absorption
F(rel) = AUC(ev1)/AUC(ev2) x Dose(ev1)/Dose(ev2)
What is the extent of absorption and how is this measured?
fraction of the dose which enters the systemic circulation, as estimated using AUC of plasma conc vs time, or from the fraction of dose excreted in urine as the active form and/or its metabolites.
What is the rate of absorption and how is this measured?
Determines the time delay between administration and the time of the maximum peak conc in the plasma being assayed (Cmax, Tmax)
What are the graphical parameters assessing F and urinary drug excretion?
F:
- Tmax = time for peak plasma conc
- Cmax = peak plasma conc
- AUC = area under the curve
Urinary excretion:
- Du = cumulative drug excreted in urine
- dDu/dt = rate of drug excreted in urine
- T = max time for urinary excretion
What factors affect F and how can this be managed in studies?
- Body weight
- Sex and age of the test subjects
- Disease states
- Genetic differences in drug metabolism
- Excretion and distribution
- Concomitant admin of other drugs
- Stress
- Time of administration of the drug
Parameters can be set when looking for candidates to reduce variation in results.
What is a generic drug?
A generic drug is a drug product that is comparable to a branded drug in terms of dosage form, strength, ROA, quality, performance characteristics and intended use.
What does a patent protection do?
Protects the investment of a drug company who developed a branded drug. Gives them the sole right to sell the durg while the patent is in effect.
When a patent protection is close to expiry, other companies can apply for authority to sell a generic version
Define pharmaceutical equivalents
Drugs are considered pharmaceutically equivalent if they
- contain the same active ingredient
- same dosage form
- same ROA
- same strength/conc
May differ in characteristics such as shape, scoring configuration, release mechanisms, packaging, excipients and labelling.
Define a pharmaceutical alternative
Drugs are considered to be alternatives if they contain the same active moiety, bit in different salt forms, esters, complexes, or are different dosage forms.
Define a therapeutic equivalent.
Therapeutic equivalents are pharmaceutically equivalent, but also expected to have the same clinical effect and safety profile when administered under conditions specified in labelling.
Define bioequivalence
Drugs having pharmaeutical and therapeutic equivalence.
Absence of significant difference in the rate and extent to which active ingredients or moieties become available at the site of dug action when administered at the same molar dose or under similar conditions in an appropriately designed study.
What is bioequivalence necessary for?
BE is necessary for generic products, where no clinical studies are performed to support its safety and efficacy. This data is extrapolated from the brand product to a generic product.
Bio-inequivalence may cause significant therapeutic difference/failure or diminished clinical safety.
When are medicines considered non-interchangeable?
- product has narrow therapeutic index (e.g. warfarin)
- product delivery system is not pharmaceutically equivalent
- no acceptable method to establish BE (topical products)
