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Jul 28,  · The first pass effect is a phenomenon in which a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation. The first pass effect is often associated with the liver, as this is a ma Author: Timothy F. Herman, Cynthia Santos. First-Pass Effect. Drugs that are administered orally (as opposed to intravenously, intramuscularly, sublingually, or transdermally) must first pass from the intestine to the liver before reaching the general circulation. Thus, for many drugs, much of the dose is reduced by xenobiotic metabolism before reaching the tissues. The first-pass metabolism or the first-pass effect or presystemic metabolism is the phenomenon which occurs whenever the drug is administered orally, enters the liver, and suffers extensive biotransformation to such an extent that the bioavailability is drastically reduced, thus showing subtherapeutic action (Chordiya et al., ). It happens. Read more