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First-pass metabolism is the breakdown of a drug before much of an absorbed dose reaches the systemic circulation. It occurs most commonly after oral administration as the drug passes through the intestinal wall and liver. The process can reduce the amount of active drug available to reach its target tissues. It is also called the first-pass effect or presystemic metabolism.
read more about firstpass metabolism ...After an oral drug is absorbed from the digestive tract, much of the blood carrying it flows through the portal vein to the liver. Enzymes in the intestinal wall and liver can metabolize part of the drug during this initial passage. The unchanged portion then enters the systemic circulation. Some metabolites are inactive, while others remain active or have different effects from the original drug.
Intravenous administration bypasses absorption and hepatic first-pass metabolism completely. Sublingual, buccal, transdermal, inhaled, and some other routes can avoid much of the initial portal passage. Rectal administration can bypass it partly, depending on where the drug is absorbed. Avoiding first-pass metabolism does not prevent the liver or other organs from metabolizing the drug later.
The extent of first-pass metabolism depends on the drug, intestinal enzymes, liver blood flow, liver function, genetics, age, and interacting substances. Food and other medicines can increase or inhibit the enzymes or transporters involved. Liver disease or reduced blood flow can raise the systemic exposure of some high-extraction drugs. Differences among patients can therefore change the effect of the same oral dose.
Strong first-pass metabolism can produce low or variable oral bioavailability. A larger oral dose can be needed than an intravenous dose to achieve similar systemic exposure. Route changes, liver impairment, or enzyme interactions can therefore require a dosing adjustment. Drug developers consider the first-pass effect when selecting formulations, routes, and recommended doses.
Most absorbed oral drugs pass through the intestinal wall and liver before entering the systemic circulation. The amount metabolized during that passage ranges from minimal to extensive.
No. An intravenous dose enters the systemic circulation directly and has complete bioavailability. It can still be metabolized by the liver after circulating through the body.
Medicine absorbed through veins under the tongue largely enters the systemic circulation without first passing through the liver. Any portion that is swallowed can still undergo intestinal and hepatic first-pass metabolism.
Yes. Age, liver disease, blood-flow changes, genetics, food, and interacting medicines can alter enzyme activity or hepatic extraction. These changes can affect drug exposure and dosing needs.
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