Bioavailability of cimetidine in man

Area of Science:

• Pharmacokinetics
• Drug bioavailability
• Gastrointestinal pharmacology

Background:

• Cimetidine is a histamine H2 receptor antagonist used to treat conditions like peptic ulcers.
• Understanding the bioavailability of different cimetidine formulations is crucial for optimizing therapeutic efficacy.
• Parenteral administration bypasses first-pass metabolism, potentially altering drug absorption compared to oral routes.

Purpose of the Study:

• To compare the bioavailability of parenteral cimetidine (intramuscular vs. intravenous) and oral cimetidine liquid.
• To assess the bioequivalence of cimetidine tablets compared to an oral liquid formulation.
• To evaluate pharmacokinetic parameters including blood levels and urinary excretion.

Main Methods:

• A balanced three-way crossover study involving 12 healthy volunteers.
• Comparison of blood levels and urinary excretion following intramuscular, intravenous, and oral administration of 300 mg cimetidine.
• A separate study assessed the bioequivalence of 300 mg cimetidine tablets versus oral liquid in another group of 12 volunteers.

Main Results:

• Intramuscular and intravenous routes of cimetidine administration exhibited virtually interchangeable bioavailability.
• Oral cimetidine liquid showed a reduced area under the blood level curve compared to parenteral doses.
• Oral liquid demonstrated equivalence in maintaining blood levels above 0.5 microgram/mL compared to parenteral routes.
• Cimetidine 300 mg tablets were found to be bioequivalent to the 300 mg oral liquid formulation.

Conclusions:

• Parenteral routes (IM/IV) of cimetidine are interchangeable for achieving systemic drug exposure.
• Oral cimetidine liquid offers comparable therapeutic potential to parenteral administration based on sustained therapeutic blood levels.
• Cimetidine tablet formulation provides equivalent bioavailability to the oral liquid, ensuring consistent therapeutic outcomes.