When a drug is given orally, it is metabolized in the intestine and the liver before reaching the systemic circulation. Such breakdown of the drug is called the first-pass effect. Soon after ingestion, the drug is absorbed by the small intestine. The intestinal enzymes metabolize some molecules, but most are transported via the blood to the liver. Within the liver, the drug can be metabolized or excreted through the bile. The fraction of drug the liver eliminates is known as the extraction ratio or ER. It is measured from the drug concentrations in blood entering and leaving the liver. If a drug is completely absorbed and minimally lost by chemical degradation, the amount remaining after the first-pass effect is its bioavailability. The greater the first-pass effect, the lower the drug's bioavailability. Drugs with high ERs are administered via sublingual and transdermal routes that provide direct access to the systemic circulation to avoid the first-pass effect.