Bioavailability (F)

• The central circulation is the reference point for all bioavailability calculations. It is the only fluid that has contact with the entire body.
• Not all drug given to an animal per os (or other non-IV routes) is absorbed into the central circulation.
• Not all of an administered dose is "available" to the sites of action.
• Bioavailability is defined as the fraction of drug administered that reaches the central circulation, i.e., the circulating post-portal venous blood.
• By definition, bioavailability for a drug administered intravenously is 100%. The "term" used is "F". An F of 1.00 is equivalent to a bioavailability of 100%.
• One can find the "Area-Under-the-Curve" (AUC) for a drug as a measure of the exposure of the animal to the drug. In its simplest form, one plots the drug concentration versus time and then adds up the areas of successive trapezoids formed under the curve. This is the so-called "trapezoidal rule".
• A fun, simple way of determining the the relative drug exposure would be to cut out the area under the plasma concentration versus time plot and weigh it.
• Find the area (weight!?) for the "test-route", e.g., PO and compare it to the area (weight!?) of an intravenous injection of the same drug dosage.
• Graphic depiction of determining F
• Some representative values of F in animals:
  • Ketamine, cat, IM, F=0.92
  • Ampicillin HCl, cat, SC, F=0.56
  • Sulfadimethoxine suspension, dog, PO, F=0.56
  • Kanamycin Sulfate, sheep, IM, F=1.00
  • Kanamycin Sulfate, sheep, Intratracheally, F=0.38
• Some drugs with low "F" in humans (F < .5) Rowland&Tozer89,p120
  • Alprenolol
  • 5-fluorouracil
  • Lidocaine
  • Morphine
  • Nifedipine
  • Propranolol
  • Salicylamide