The first-pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption which is generally related to the liver and gut wall. Notable drugs that experience a significant first-pass effect are imipramine, morphine, propranolol, buprenorphine, diazepam, midazolam, demerol, cimetidine, and lidocaine.
After a drug is swallowed, it is absorbed by the digestive system and enters the hepatic portal system. It is carried through the portal vein into the liver before it reaches the rest of the body. The liver metabolizes many drugs, sometimes to such an extent that only a small amount of active drug emerges from the liver to the rest of the circulatory system. This first pass through the liver thus greatly reduces the bioavailability of the drug. Alternative routes of administration like suppository, intravenous, intramuscular, inhalational aerosol and sublingual avoid the first-pass effect because they allow drugs to be absorbed directly into the systemic circulation.--wikipedia
Morphine oral Bioavailability：Oral: 20% to 40%
Peak levels after oral administration are much lower than after parenteral routes, since oral M undergoes extensive first-pass metabolism in the liver. With repeated administration, the oral-parenteral relative potency ratio is 1:3 M can be administered epidurally or intrathecally and has also been given intracerebroventricularly.
-- Therapeutic Drug Monitoring [1991, 13(1):1-23], Clinical pharmacokinetics of morphine.
Atropine oral Bioavailability：Oral Availability：50%
-- Applied Biopharmaceutics & Pharmacokinetics, table E.1
Propranolol：50% to 70% of an oral dose is metabolized in the liver during its first pass (Cleveland & Shand, 1972).
Benazepril： is unsuitable for oral administration due to poor absorption：Oral: 37%
MOTOFEN(difenoxin hydrochloride and atropine sulfate) Tablet
Difenoxin (as the hydrochloride) . . .. . . . . . . . . . . . . . . . . . . .1.0 mg
Atropine Sulfate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .0.025 mg
management of acute nonspecific diarrhea and acute exacerbations of chronic functional diarrhea.
Belladonna Alkaloids with Phenobarbital
（phenobarbital/ hyoscyamine/ atropine/scopolamine) 0.0194 mg-0.1037 mg-16.2 mg-0.0065 mg）
用途：IBS、acute enterocolitis、duodenal ulcer。