Drug absorbed from the gut passes through the liver before reaching the systemic circulation
Expansion
Drug absorbed from the stomach and intestine enters the portal vein and traverses the liver before reaching the systemic circulation. Metabolism there, plus metabolism in the gut wall itself, reduces the fraction reaching the target: bioavailability.
Drugs with extensive first pass metabolism include glyceryl trinitrate, propranolol, morphine, lidocaine, verapamil and levodopa, which is why their oral doses greatly exceed intravenous ones, and why lidocaine cannot be given orally at all.
Routes that bypass it
- Sublingual and buccal: drain to the superior vena cava
- Rectal (lower third): drains to the internal iliac veins, so about half bypasses the liver
- Transdermal, inhaled, intranasal
- Parenteral
Clinical corollaries: glyceryl trinitrate is given sublingually for exactly this reason; liver disease and portosystemic shunting raise the bioavailability of these drugs, so doses must be reduced; and grapefruit juice inhibits intestinal CYP3A4, raising the bioavailability of several drugs unpredictably.