First-pass metabolism

First-pass metabolism, also called the first-pass effect, is the loss of part of a drug dose before it reaches the rest of the body. A swallowed drug is absorbed mostly in the small intestine and carried by the hepatic portal vein straight to the liver. Enzymes in the intestinal wall and, above all, liver enzymes such as the cytochrome P450 family can break down a share of it on this first passage, so less active drug enters the systemic circulation.

The effect is a major reason why bioavailability after oral dosing is often well below 100 percent, and why an oral dose is frequently larger than an intravenous dose of the same drug. For some drugs so little survives that they cannot be given by mouth at all. Its strength varies with liver health, genes and other medicines that speed up or slow down liver enzymes.

Routes that bypass the portal circulation avoid it. Intravenous injection skips it completely, and drugs placed under the tongue or against the cheek are absorbed into veins that drain into the general circulation. Rectal dosing avoids it only in part. Nitroglycerin for chest pain is a classic drug given under the tongue for this reason.