Rectal versus oral absorption of codeine phosphate in man

Area of Science:

• Pharmacokinetics
• Drug Delivery Systems
• Gastroenterology

Background:

• Codeine phosphate is commonly administered orally for pain relief.
• Rectal drug administration offers an alternative route, potentially bypassing first-pass metabolism.
• Evaluating rectal dosage forms is crucial for optimizing drug delivery and patient outcomes.

Purpose of the Study:

• To compare the rectal absorption of codeine phosphate from different dosage forms (aqueous solutions, fatty suppositories) with oral administration.
• To assess the plasma concentration profiles and bioavailability of codeine phosphate via rectal versus oral routes.
• To investigate the absorption rate characteristics of rectal codeine phosphate formulations.

Main Methods:

• A cross-over study involving 7 healthy volunteers.
• Administration of a single 60 mg dose of codeine phosphate via oral solution, rectal aqueous solution, and rectal fatty suppository.
• Quantification of plasma codeine concentrations using High-Performance Liquid Chromatography (HPLC).

Main Results:

• Rectal administration (aqueous solution or fatty suppository) resulted in plasma concentration profiles nearly identical to oral dosing.
• Bioavailability was comparable across all tested rectal and oral dosage forms.
• Rectal absorption from an alkaline solution demonstrated a significantly faster rate (P < 0.05) compared to oral administration.

Conclusions:

• Rectal dosage forms of codeine phosphate offer comparable bioavailability to oral administration.
• Alkaline rectal solutions may provide a faster onset of action for codeine phosphate compared to oral routes.
• Rectal administration is a viable alternative for codeine phosphate delivery, with potential for accelerated absorption.