3.20 : 薬物吸収に影響を与える要因：全身前排除（Pre-systemic Elimination）

Most oral drugs are absorbed from the intestines into the hepatic portal vein, passing through the liver before entering the systemic circulation. This leads to pre-systemic elimination, also known as the first-pass effect.

Soon after entering the liver, they are metabolized or excreted into the bile, decreasing their bioavailability or the accessible drug fraction in circulation.

The amount of the drug excreted from the liver is called the liver extraction ratio or ER,  measured by drug concentration in the blood entering and exiting the liver.

Notably, ER depends on changes in the hepatic blood clearance and flow, altering the drug's bioavailability.

Drugs with a high extraction ratio undergo extensive pre-systemic metabolism, leading to poor oral bioavailability. So, higher doses are required to achieve an adequate therapeutic response. 

Additionally, alternative routes bypass pre-systemic elimination and deliver directly to the systemic circulation.

For instance, upon oral ingestion, 90% of nitroglycerin undergoes pre-systemic elimination. So nitroglycerin is often given sublingually to bypass pre-systemic metabolism.