When an active ingredient is absorbed into the bloodstream from the gastrointestinal tract, it is significantly metabolised in the liver before it reaches the systemic circulation, this phenomenon is known as the "first pass effect." In other words, the liver metabolises and excretes a portion of it before it reaches the body's target site.

Active ingredients taken orally are absorbed into the portal circulation, or the blood supply that feeds the liver, before being distributed to the rest of the body, which results in the first pass effect. The amount that is available to exert its desired effect is decreased because the liver enzymes break down some of it before it enters the systemic circulation.

The extent of the first pass effect varies depending on the active ingredient as well as personal elements like genetics and liver function. Some have a high first pass effect, which means that a sizeable amount is metabolised before it enters the systemic circulation. Others, in contrast, have a low first pass effect, which means that their liver metabolism is minimal before they reach the bloodstream as a whole.

The efficacy and safety of the active ingredient can be affected by the first pass effect. Hence it may also affect the active ingredient's chosen route of administration. For instance, it might be necessary to administer active ingredients with a high first pass effect via an alternative route, like injection, or a painless and fuss-free, non-invasive method like KPLASS' transdermal skin patch.