Bioavailability from various galenic formulations of flunitrazepam.

Area of Science:

• Pharmacokinetics
• Drug Formulation
• Clinical Pharmacology

Background:

• Flunitrazepam (Rohypnol) is a benzodiazepine with various administration routes.
• Understanding bioavailability across different formulations is crucial for effective therapeutic use.

Purpose of the Study:

• To determine the absolute and relative bioavailability of flunitrazepam in tablet, oral solution, and suppository formulations.
• To compare the pharmacokinetic profiles of different flunitrazepam delivery methods.

Main Methods:

• A cross-over study involving 6 healthy volunteers.
• Analysis of plasma concentrations using a three-compartment pharmacokinetic model.

Main Results:

• Flunitrazepam tablets and oral solutions demonstrated bioequivalence, with at least 80% absorption.
• Flunitrazepam suppositories exhibited approximately 50% bioavailability.
• A three-compartment model described plasma concentrations, with slow reflux from the third compartment being rate-limiting for elimination.

Conclusions:

• Oral flunitrazepam formulations (tablet, solution) are bioequivalent.
• Suppository formulation significantly reduces flunitrazepam bioavailability compared to oral routes.
• Pharmacokinetic analysis reveals a multi-compartment distribution and elimination process for flunitrazepam.