Absorption and Relative Bioavailability Flashcards Preview

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Flashcards in Absorption and Relative Bioavailability Deck (10):

What is bioavailability?

The fraction of the dose which reaches systemic circulation as intact drug


What is absolute bioavailability compared to?

Absolute bioavailability compares the absolute extent of absorption of a given formulation and route of administration to an intra-venous dose


What is relative bioavailability compared to?

  • relative bioavailability compares the extent of absorption of a given formulation and route of administration relative to an alternative formulation/route
    • For example, one could compare oral administration to intra-muscular (im) administration


Does relative bioavailability provide any direct information about absolute bioavailability?



Is it possible for relative bioavailability to exceed 100%?

Yes, the reference formulation/route might have a low absolute bioavailability (eg 10%) while the comparator might have a high absolute bioavailability (eg 100%).  In this case the relative bioavailability would be (100/10) = 10 (ie. 1000%)


Is it possible to infer some estimate of absolute bioavailability of a formulation or route?

  • Yes, but only if one knows the absolute bioavailability of one of the alternative routes
    • For example, the relative bioavailability of im to oral administration is 2.0.  If one knows the absolute bioavailability of the oral route is 50%, then one could estimate that the absolute bioavailability of the im route is ~100% (ie. 50% x 2.0)


Who are generic drugs produced by?

  • Generic drugs are produced by companies when the original "brand name" has it's patent expired
  • These are allowed to be marketed if they provide an "equivalent" exposure and time-course of exposure to the original


What are generic drugs assessed by to see if they provide an "equivalent" exposure and time-courseof exposure to the original?

  • Assessed by bioequivalence
    • refers to formulations of a drug with rates and extents of absorption that are sufficiently similar that there are not likely to be any clinically important differences with respect to either efficacy or safety
    • is the AUC (extent of exposure) and Cmax (extent and time-course of exposure) and Tmax (time-course of exposure) and the variability in exposure between people (90% confidence intervals) within 80-125% of the original marketed formulation.  In essence this is assessing the relative bioavailability (AUC)


What is the Biopharmaceutic Classification System (BCS)?

  • Can be used by a company to attempt to avoid a clinical trial to prove bioequivalence (ie. save  a lot of time and money)
    • If the drug is in Class 1 (highly soluble and highly permeable)
      • absorption will be high and really only limited by the dissolution characteristics of the formulation
    • If the drug has a wide therapeutic index (ie. a large safety margin between efficacy and toxicity)
    • formulation can be shown in vitro to be rapid and comparable to the original, then the company can apply for a "bio waiver"


What is a biowaiver?

A bio waiver is permission to not perform a clinical bioequivalence trial, and market their product. There are other criteria (and strict definitions) well, but this is the essence of the process