In the discussion of extravascular administration, it mentioned that it is possible that not all of the administered dose of a drug is absorbed. The percentage of the dose that is absorbed and reaches the circulation is called the bioavailability (F). A drug's bioavailability is typically less than 100. This can be due to poor absorption, or more commonly, metabolic degradation prior to the reaching the systemic circulation. Drugs given enterally pass through the portal vein and the liver prior to reaching the systemic circulation.
The bioavailability can be calculated by giving a drug both intravenously and orally. When the AUC is calculated (see calculating clearance) in both situations, and when it can be assumed that intravenous clearance is the same as oral clearance, this will allow calculation of the amount absorbed.
F = AUCoral / AUCintravenous
See how bioavailability effects the AUC by clicking here and selecting the AUC (module 3).
A certain drug can be administered intravenously and orally. The oral bioavailability is 0.5. What is expected if that drug is taken orally instead of intravenously? (Multiple answers possible)
Extra info: The bioavailability is defined as F = AUC(oral) / AUC(intravenous). If F=0.5, for a same dose the AUC will therefore be halved, and the dose needs to be doubled for oral delivery to obtain the same number of molecules that enter the systemic circulation, and to obtain the same AUC. Also, the total exposure (the interpretation of AUC) of oral delivery is 0.5 times the exposure of intravenous administration. The elimination rate is unaffected, so half-life is unaffected too.
For a drug with Foral = 0.5, the maximum concentration (Cmax) is always 50% of the Cmax of intravenous administration
Extra info: This is NOT true when absorption is slow. In those circumstances, the Cmax of oral administration will be lower than 50% compared to intravenous administration, because during the absorption phase also elimination takes place and drug is already eliminated before Cmax is reached. Therefore with F = 0.5, the maximum Cmax than can be reached is 50% of intravenous administration, but only when the absorption rate is very high compared ot the elimination rate, otherwise.
A new drug is tested using 2 different administration routes:
- 80 mg oral
- 20 mg intravenous
The AUC's of both administered drugs are:
- oral: 1200 ng/mL*h
- intravenous: 1500 ng/mL*h
What is the oral bioavailability of this drug?
Extra info: The oral Bioavailability can be calculated via a (dose corrected) AUC-ratio of both administered drugs: (AUC(oral) / AUC(iv)) * (Dose(iv) / Dose(oral)) = 1200/1500 * 20/80 = 0.2 (20%)