The fraction of a dose reaching the systemic circulation unchanged
Expansion
Bioavailability (F) is the fraction of a dose reaching the systemic circulation unchanged. Intravenous F = 1 by definition.
Routes that bypass the liver, avoiding first pass metabolism:
- Sublingual and buccal, draining to the superior vena cava. GTN, buprenorphine
- Rectal, partially: the lower rectum drains systemically, the upper rectum to the portal system
- Transdermal: fentanyl, HRT, nicotine
- Inhaled, intranasal, intravenous, intramuscular and subcutaneous
Drugs with extensive first pass metabolism need much larger oral doses, or cannot be given orally at all: GTN, propranolol, morphine, levodopa, lidocaine, verapamil.
“Morphine oral to intravenous is about 2 to 1; codeine and tramadol are closer to 1 to 1.”
Factors altering bioavailability: gastric pH and food, gut motility, formulation, P-glycoprotein efflux, gut wall and hepatic enzymes, and liver disease or portosystemic shunting, which raises the bioavailability of high extraction drugs and can cause toxicity at ordinary doses.
Grapefruit juice inhibits intestinal CYP3A4, raising levels of simvastatin, amlodipine and ciclosporin.