Additional Pharmacokinetic Parameters

Bioavailability

Bioavailability (designated as F) is defined as the fraction of the administered drug reaching the systemic circulation as intact drug. Bioavailability is highly dependent on both the route of administration and the drug formulation. For example, drugs that are given intravenously exhibit a bioavailability of 1, since the entire dose reaches the systemic circulation as intact drug. However, for other routes of administration, this is not necessarily the case.

Subcutaneous, intramuscular, oral, rectal, and other extravascular routes of administration require that the drug be absorbed first, which can reduce bioavailability. The drug also may be subject to metabolism prior to reaching the systemic circulation, again potentially reducing bioavailability. For example, when the p-blocking agent propranolol is given intravenously, F = 1, but when it is given orally, F = ~0.2, suggesting that only approximately 20% of the administered dose reaches the systemic circulation as intact drug.

With respect to the effect of drug formulation on bioavailability, the drug digoxin provides a good example. Given orally as a solution, the bioavailability of digoxin approaches F = 1, suggesting essentially complete bioavailability and one that approaches that of the intravenous formulation. Digoxin liquid capsules also exhibit F = ~1 when given orally and thus are also completely available. However, for digoxin tablets, F = ~0.7, suggesting incomplete bioavailability, probably because of lack of absorption.

Two types of bioavailability can be calculated, depending on the formulations available and the information required. The gold standard is a calculation of the absolute bioavailability of a given product compared to

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