Bioavailability and First Pass Metabolism

Summary

This video discusses the first-pass effect and bioavailability of drugs taken orally. It explains how drugs move from the digestive tract to the hepatic portal system and are metabolized in the liver before reaching systemic circulation. Many drugs have a 'heavy' first-pass effect, resulting in significant loss of the drug before it reaches the bloodstream, requiring alternative administration routes like intravenous or sublingual. The video provides an example calculation, showing how to determine the overall bioavailability of a drug based on absorption and liver metabolism rates.

Takeaways

• 💊 The first pass effect refers to the drug's journey from the digestive tract to the liver before entering systemic circulation.
• 🩸 Drugs taken orally pass through the digestive tract and enter the hepatic portal system, which includes capillaries and the hepatic portal vein.
• 🧬 The liver plays a major role in metabolizing drugs, which can reduce the amount of drug that reaches systemic circulation.
• ⚠️ Some drugs experience a heavy first pass effect, meaning much of the drug is destroyed in the liver before entering circulation.
• 💉 Drugs with a heavy first pass effect may be administered through alternative routes such as intravenous, sublingual, or transdermal.
• ❤️ Nitrates, used for treating angina, have a heavy first pass effect and are often administered sublingually or intravenously to avoid liver metabolism.
• 🔢 Bioavailability is the percentage of a drug that reaches systemic circulation; intravenous drugs are 100% bioavailable.
• 📉 Oral drugs are not fully bioavailable due to incomplete absorption and destruction by the liver.
• 🧮 To calculate bioavailability, multiply the percentage absorbed (FG) by the percentage that escapes liver metabolism (FH).
• 📊 In an example where 300 mg of a drug is taken, with 70% absorption and 60% hepatic extraction, the overall bioavailability is 28%, resulting in 84 mg reaching systemic circulation.

Q & A

What is the first pass effect in drug metabolism?

The first pass effect refers to the metabolism of a drug that occurs in the liver before the drug reaches systemic circulation. When a drug is taken orally, it first passes through the digestive tract and into the hepatic portal system, where a significant portion can be metabolized by the liver before entering the bloodstream.

Why do some drugs need alternative routes of administration other than oral intake?

Some drugs have a heavy first pass effect, meaning that a large portion of the drug is metabolized and destroyed by the liver before it can reach systemic circulation. For such drugs, alternative routes like intravenous, sublingual, or transdermal administration are used to bypass the liver and ensure that more of the drug reaches the bloodstream.

What is bioavailability, and how is it measured?

Bioavailability is the fraction or percentage of a drug that reaches systemic circulation after administration. It is measured as a percentage, with drugs administered intravenously being 100% bioavailable because they directly enter the bloodstream, while orally administered drugs usually have lower bioavailability due to absorption and first pass metabolism.

How does the hepatic extraction ratio affect drug bioavailability?

The hepatic extraction ratio represents the percentage of a drug that is removed by the liver during first pass metabolism. A high hepatic extraction ratio means that the liver metabolizes a large portion of the drug before it reaches systemic circulation, reducing bioavailability.

What is the formula used to calculate overall bioavailability?

The overall bioavailability (F) of a drug is calculated by multiplying FG (the fraction of the drug absorbed into portal circulation from the gut) by FH (the fraction of the drug that escapes the liver and enters systemic circulation).

In the example provided, how much of the 300 mg drug dose makes it to systemic circulation?

In the example, 70% of the 300 mg dose is absorbed into portal circulation, and 40% escapes the liver (since the hepatic extraction ratio is 60%). The overall bioavailability is 28%, meaning that 84 mg of the drug reaches systemic circulation.

What does a hepatic extraction ratio of 60% mean?

A hepatic extraction ratio of 60% means that 60% of the drug is metabolized and removed by the liver before it can enter systemic circulation, leaving 40% available for distribution throughout the body.

Why are intravenous drugs 100% bioavailable?

Intravenous drugs are 100% bioavailable because they are injected directly into the bloodstream, bypassing the digestive system and the liver, so the entire dose enters systemic circulation.

What is an example of a drug class with a heavy first pass effect?

Nitrates, which are used to treat chest pain (angina), are an example of a drug class with a heavy first pass effect. They are metabolized extensively by the liver when taken orally, so they are often administered by alternative routes like sublingually or intravenously.

What are some alternative routes of drug administration to avoid the first pass effect?

Alternative routes of drug administration to bypass the first pass effect include intravenous, rectal, subcutaneous, intramuscular, inhaled, transdermal, sublingual, buccal, aural, intra-arterial, intranasal, intraocular, intravaginal, and intra-articular.