Lecture on First Pass Effect and Bioavailability

Key Concepts

• First Pass Effect:

  • Refers to the process where a drug taken orally passes through the digestive tract into the hepatic portal system.
  • The hepatic portal system includes capillary networks around digestive organs and the hepatic portal vein that carries absorbed materials to the liver.
  • The liver metabolizes drugs, often reducing the amount of active drug that reaches systemic circulation.
  • This phenomenon is known as "first pass metabolism".

• Bioavailability:

  • Defined as the fraction or percentage of a drug that reaches systemic circulation.
  • Drugs administered intravenously have 100% bioavailability.
  • Oral drugs often have less than 100% bioavailability due to absorption inefficiencies and first pass metabolism.

First Pass Effect Details

• Heavy First Pass Effect:
  • Some drugs are significantly broken down by the liver, resulting in minimal systemic availability when taken orally.
  • Alternative administration routes are used for these drugs, such as:
    • Intravenous, rectal, subcutaneous, intramuscular, inhaled, transdermal, sublingual, buccal, aural, intra-arterial, intranasal, intraocular, intravaginal, and intra-articular.
  • Example: Nitrates used for treating angina have a heavy first pass effect.
    • They are administered sublingually, topically, or intravenously.

Calculating Bioavailability

• Equation for Bioavailability (F):

  • F = FG * FH
  • FG = fraction of drug absorbed into portal circulation.
  • FH = fraction of absorbed drug that escapes first pass metabolism by the liver.

• Example Problem:

  • Given:
    • 300 mg of a drug administered orally.
    • 70% of the drug absorbed (FG).
    • Hepatic extraction ratio: 60%.
  • Calculation:
    • FH = 100% - hepatic extraction ratio = 40%.
    • F = 70% * 40% = 28%.
    • Amount reaching systemic circulation = 28% of 300 mg = 84 mg.

Assessment Question

• A question was provided to assess understanding of the first pass effect, reinforcing the concept discussed.

Conclusion

• Understanding the first pass effect and bioavailability is crucial in pharmacology, as it influences drug administration routes and effectiveness.