📘 Medicinal Pharmaceutical Chemistry – Lecture 6 First Pass Metabolism & Bioavailability (Easy to Understand • Exam-Oriented • Highly Engaging)

 🌟 Introduction

Have you ever thought 🤔

👉 Why some drugs are not given orally?

👉 Why the same dose works differently when given by different routes?

The answer lies in First Pass Metabolism and Bioavailability —

one of the most scoring and concept-based topics for B.Pharm Semester 4.

If you understand this lecture well, pharmacokinetics becomes very easy 💡

🧠 What is First Pass Metabolism?

First Pass Metabolism (also called First Pass Effect) is the metabolism of a drug before it reaches systemic circulation.

📌 Where does it occur?

• Intestinal wall

• Liver (main site)

📌 Exam definition (write this):

First pass metabolism is the biotransformation of a drug in the liver or intestinal wall after oral administration, resulting in reduced drug concentration in systemic circulation.

🔄 How First Pass Effect Occurs? (Step-by-Step)

1️⃣ Drug is taken orally

2️⃣ Absorbed from GIT

3️⃣ Enters portal circulation

4️⃣ Reaches liver

5️⃣ Metabolized before reaching blood

👉 Result: Reduced drug availability

💊 Drugs with High First Pass Metabolism

Some drugs are extensively metabolized in the liver, so their oral bioavailability is very low.

📌 Important Examples:

• Nitroglycerin

• Propranolol

• Lidocaine

• Morphine

👉 That’s why Nitroglycerin is given sublingually, not orally.

⭐ Very common viva + MCQ point

❌ How to Avoid First Pass Metabolism?

Doctors use alternative routes to bypass the liver initially.

Routes that avoid first pass effect:

✔ Sublingual

✔ Buccal

✔ Intravenous

✔ Transdermal

✔ Rectal (partially)

📌 Exam-friendly line:

Non-oral routes bypass first pass metabolism and increase bioavailability.

📊 What is Bioavailability?

Bioavailability (F) is the fraction of administered drug that reaches systemic circulation in unchanged form.

📌 Definition for exam:

Bioavailability is the rate and extent to which a drug is absorbed and becomes available at the site of action.

📈 Factors Affecting Bioavailability

✔ First pass metabolism

✔ Drug formulation

✔ Route of administration

✔ Drug solubility

✔ Stability in GIT

🧮 Bioavailability Formula (Very Important)

$$F = \frac{AUC_{oral}}{AUC_{IV}} \times 100$$

📌 Where:

• AUC = Area Under Curve

👉 IV route = 100% bioavailability

🔬 Clinical Significance

Understanding first pass metabolism helps in:

✔ Dose adjustment

✔ Route selection

✔ Avoiding therapeutic failure

✔ Designing better drug delivery systems

🧠 Difference Between First Pass Effect & Bioavailability

Feature	First Pass Effect	Bioavailability
Meaning	Drug metabolism before circulation	Amount of drug reaching blood
Effect	Reduces drug level	Indicates drug availability
Relation	Cause	Result

✍️ Exam Answer 

First pass metabolism reduces the amount of drug reaching systemic circulation after oral administration, thereby decreasing bioavailability. Drugs with extensive first pass metabolism are given by alternative routes to achieve therapeutic effect.

⭐ Write this → full marks

🧩 MCQ Section (Student Engagement)

Q. Which route avoids first pass metabolism completely?

A) Oral

B) Rectal

C) Sublingual ✔

D) Intramuscular

👉 Answer in comments!

📌 Question:

Why is nitroglycerin given sublingually and not orally?

👇 Comment your answer below.

🔗 Internal Linking 

• Lecture 3 Physicochemical properties of drugs and their role in drug action

• Lecture 4:Drug Metabolism (Biotransformation): Phase I & Phase II — The Easiest Explanation Ever!

• Lecture 5: Factors Affecting Drug Metabolism Including Stereochemical Aspects (Medicinal Pharmaceutical Chemistry – Semester IV)

• Lecture 7: Drug Clearance & Half-life (Coming Next)

📌 Bookmark this page for future lectures