•Metabolism that occurs in the liver and intestinal wall before it reaches the blood streamand site of action
•The drug is taken from the digestive system, through the portal vein to the liver, where drugs are significantly metabolized leaving only a small amount of active drug to enter the bloodstream
•Greatlydecreased the bioavailability of the drug
•Oral administration is subject to first pass effect
•Drugs that are more affected by first pass metabolism will have a much higher oral dose than IV dose
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