FIRST PASS METABOLISM
High‑Yield Pharmacology Notes for Exams, Tests & Quick Revision
Course: Pharmacology (Undergraduate)
Document type: Exam‑ready lecture summary with clinical examples
INTRODUCTION
First pass metabolism refers to the metabolism of a drug at a specific site in the body that results in a
reduced concentration of the active drug reaching the systemic circulation. This phenomenon mainly affects
orally administered drugs and significantly lowers their bioavailability.
First pass metabolism primarily occurs in the gastrointestinal tract, intestinal wall, liver, lungs, and
vasculature. Because a substantial portion of the drug is metabolized before reaching systemic circulation,
higher oral doses are often required.
Routes that bypass first pass metabolism: - Intravenous (IV) - Intramuscular (IM) - Sublingual -
Transdermal - Inhalation - Suppositories
ATTRIBUTES OF DRUGS WITH HIGH FIRST PASS METABOLISM
• Require higher oral doses compared to parenteral or sublingual routes
• Show marked individual variation in dosage due to age and gender
• Increased oral bioavailability in liver disease (e.g. liver cirrhosis)
• Increased bioavailability when administered with drugs competing for metabolism (e.g. propranolol
and chlorpromazine)
EVIDENCE OF FIRST PASS EFFECT (EXAM‑FREQUENT)
• Low concentration of parent drug in systemic circulation after oral administration
• High variability in bioavailability between individuals
• Different metabolites formed depending on route of administration
• Clinically important when metabolites are pharmacologically active or toxic
1
High‑Yield Pharmacology Notes for Exams, Tests & Quick Revision
Course: Pharmacology (Undergraduate)
Document type: Exam‑ready lecture summary with clinical examples
INTRODUCTION
First pass metabolism refers to the metabolism of a drug at a specific site in the body that results in a
reduced concentration of the active drug reaching the systemic circulation. This phenomenon mainly affects
orally administered drugs and significantly lowers their bioavailability.
First pass metabolism primarily occurs in the gastrointestinal tract, intestinal wall, liver, lungs, and
vasculature. Because a substantial portion of the drug is metabolized before reaching systemic circulation,
higher oral doses are often required.
Routes that bypass first pass metabolism: - Intravenous (IV) - Intramuscular (IM) - Sublingual -
Transdermal - Inhalation - Suppositories
ATTRIBUTES OF DRUGS WITH HIGH FIRST PASS METABOLISM
• Require higher oral doses compared to parenteral or sublingual routes
• Show marked individual variation in dosage due to age and gender
• Increased oral bioavailability in liver disease (e.g. liver cirrhosis)
• Increased bioavailability when administered with drugs competing for metabolism (e.g. propranolol
and chlorpromazine)
EVIDENCE OF FIRST PASS EFFECT (EXAM‑FREQUENT)
• Low concentration of parent drug in systemic circulation after oral administration
• High variability in bioavailability between individuals
• Different metabolites formed depending on route of administration
• Clinically important when metabolites are pharmacologically active or toxic
1
