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Metabolism of pholcodine in man
1Institute of Pharmacology and Toxicology, University of Saarland, Homburg/Saar, Fed. Rep. of Germany.
Arzneimittel-Forschung
|May 1, 1990
Summary
This study investigated the metabolism of pholcodine, an antitussive drug. Pholcodine and its metabolites are eliminated slowly due to low metabolism, with pholcodine detectable in urine for weeks.
Area of Science:
- Pharmacology
- Drug Metabolism
- Analytical Chemistry
Background:
- Pholcodine is an antitussive agent.
- Understanding its metabolic fate is crucial for clinical use.
Purpose of the Study:
- To identify and characterize the human metabolites of pholcodine.
- To elucidate the metabolic pathways of pholcodine.
- To investigate the elimination kinetics of pholcodine and its metabolites.
Main Methods:
- Human urine samples were analyzed using gas chromatography-mass spectrometry (GC-MS).
- Metabolites were identified after enzymatic hydrolysis, extraction, and acetylation.
- Pholcodine and its metabolites were quantified over time.
Main Results:
- Seven pholcodine metabolites were identified: Nor-P, desmorpholino-hydroxy-P, nor-desmorpholino-hydroxy-P, hydroxy-P, oxo-P, nor-oxo-P, and trace amounts of morphine.
- Four metabolic pathways were proposed: N-demethylation, N-desalkylation, morpholino ring oxidation, and O-desalkylation.
- Pholcodine and its metabolites showed limited conjugation, except for morphine.
- Pholcodine was detected in urine for 5-7 weeks, while the desmorpholino-hydroxy metabolite persisted for 1-2 weeks.
Conclusions:
- The low metabolism of lipophilic pholcodine contributes to its very slow elimination.
- The identified metabolites and pathways provide insight into pholcodine's pharmacokinetic profile.