First-pass metabolism

Definition

First-pass metabolism is the process by which the concentration of a drug is significantly reduced before it reaches systemic circulation, primarily due to the metabolism that occurs in the liver. This phenomenon is crucial in pharmacokinetics, as it influences the bioavailability of orally administered medications and can determine their therapeutic effectiveness. The extent of first-pass metabolism can vary widely among different drugs and between individuals, impacting how much of the active substance reaches the bloodstream.

5 Must Know Facts For Your Next Test

1. First-pass metabolism primarily occurs in the liver but can also happen in the intestines before drugs enter systemic circulation.
2. Drugs with high first-pass metabolism may require higher oral doses to achieve effective therapeutic levels compared to those with low or minimal first-pass effects.
3. Not all drugs undergo significant first-pass metabolism; some can bypass this process and achieve higher bioavailability when taken orally.
4. Factors such as age, genetics, diet, and liver function can influence the rate and extent of first-pass metabolism for different individuals.
5. Alternative routes of administration, like intravenous or sublingual, can be used to bypass first-pass metabolism and enhance drug efficacy.

Review Questions

• How does first-pass metabolism affect the bioavailability of orally administered drugs?
  • First-pass metabolism significantly reduces the bioavailability of orally administered drugs because a portion of the drug is metabolized in the liver before it reaches systemic circulation. This means that less active drug enters the bloodstream, necessitating higher oral doses for achieving therapeutic effects. Understanding this relationship is essential for optimizing drug dosages and ensuring effective treatment outcomes.
• What role does the hepatic portal system play in first-pass metabolism, and why is it important?
  • The hepatic portal system transports blood from the gastrointestinal tract directly to the liver after a drug is absorbed. This anatomical feature is crucial because it allows for the initial metabolization of drugs before they enter general circulation. As a result, substances that undergo significant first-pass metabolism can have their pharmacological effects altered based on how much active drug remains after passing through the liver.
• Analyze how individual differences in enzyme activity can impact first-pass metabolism and drug therapy outcomes.
  • Individual differences in enzyme activity can lead to significant variations in first-pass metabolism among patients. Factors such as genetic polymorphisms in liver enzymes, concurrent medications that induce or inhibit these enzymes, and lifestyle factors like diet can all influence how a drug is metabolized. Consequently, these variations can affect therapeutic outcomes; patients with faster metabolism may require higher doses to achieve desired effects, while those with slower metabolism may experience adverse effects from standard doses due to increased drug levels in circulation.

Related terms

Bioavailability:

The fraction of an administered dose of unchanged drug that reaches systemic circulation, reflecting the efficiency of absorption and first-pass metabolism.

Hepatic Portal System: The venous system that carries blood from the gastrointestinal tract and spleen to the liver, playing a key role in first-pass metabolism.

Enzyme Induction: A process where certain substances increase the activity of drug-metabolizing enzymes in the liver, potentially enhancing first-pass metabolism.