Introduction to PK - BioAvailability & BioEquivalence
In the previous video, I showed you the different routes of administration of a drug. Apart from the intravenous route of administration, most other routes of dosing suffer some potential loss of absorption.
In this video we will look at variable extent of absorption that occurs following the commonest mode of administration, that is oral administration.
The orally administered drug actually undergoes a rather tortuous journey before it eventually enters the systemic circulation.
Firstly the drug formulation has to break apart and finally enter into solution before the absorption process can take place.
There’s always the potential for some drug to be lost at every step of the process. Some drug is lost even during the absorption from the intestinal lumen into the portal venous system, which forms the drainage of the gastrointestinal tract.
Drug molecules then face an even more formidable barrier, the liver. During passage through the liver, even more drug is lost due to the metabolic action of liver enzymes. This is called the first pass metabolism. A final fraction of administered drug eventually makes its way into the systemic circulation.
This final fraction of the administered drug that eventually makes it to the systemic circulation, constitutes the Bioavailability of the drug.
Bioavailability of usually measured by comparing the areas under the plasma concentration curve of the oral dose against that of the same dose given intravenously, which represents 100% absorption.
Loss of bioavailability can occur through a variety of mechanisms, such as loss of solubility or acid destruction in the stomach. Or it may be metabolically degraded by enzymes in the intestinal lumen or linings. The most impactful is usually the metabolic degradation that occurs in the liver.
What is the impact of a change in bioavailability on the pharmacokinetics of a drug? That’s very easy to answer, changing the bioavailability is really like changing the dose of a drug. The pharmacokinetic profile just changes proportionately up or down, depending on whether the bioavailability increases or decreases.
Different formulations of the same drug may have different bioavailabilities.
BioEquivalence is a concept of comparing the rate and extent of absorption of a generically formulated drug against that of the original or proprietary version of the drug.
Usually this is done through a comparison of their bioavailabilities.
Bioequivalence is an important concept as it establishes the clinical and therapeutic equivalence between generic versions of the drug versus that of the original invention. The primary reason is so that these generic versions of the drug may be deemed substitutable for the original proprietary version of the drug.
Don’t go away just yet. In the next short video, we will look at the post absorption events, largely the Distribution of drugs throughout the body and the relevance of the Volume of Distribution. I’ll see you guys then.
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