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Clonazepam acetylation in fast and slow acetylators
Clinical Pharmacology and Therapeutics
|September 1, 1981
Summary
The study found that individuals who are slow acetylators (SAs) excrete more of a clonazepam metabolite (7-AM) and less of its acetylated form (7-ACT) compared to rapid acetylators (RAs). This indicates that acetylator phenotype influences clonazepam metabolism.
Area of Science:
- Pharmacogenetics
- Drug Metabolism
- Clinical Pharmacology
Background:
- Acetylator phenotype significantly impacts drug metabolism.
- Clonazepam is metabolized via nitroreduction and subsequent N-acetylation.
- Understanding inter-individual variability in drug response is crucial.
Purpose of the Study:
- To investigate the role of acetylator phenotype in the biotransformation of clonazepam.
- To quantify the excretion of clonazepam metabolites in slow and rapid acetylators.
Main Methods:
- Sulfamethazine phenotyping was used to classify subjects into slow acetylators (SAs) and rapid acetylators (RAs).
- A 2-mg oral dose of clonazepam was administered to both groups.
- Urine samples were collected over 96 hours and analyzed for clonazepam, 7-amino clonazepam (7-AM), and 7-acetamido clonazepam (7-ACT).
Main Results:
- Slow acetylators excreted significantly more 7-AM (22.7% +/- 5.0%) compared to rapid acetylators (13.6% +/- 4.1%).
- Rapid acetylators excreted significantly more 7-ACT (3.9% +/- 1.8%) compared to slow acetylators (1.5% +/- 0.4%).
- These differences were statistically significant (p < 0.02).
Conclusions:
- The rate of N-acetylation of 7-amino clonazepam (7-AM) to 7-acetamido clonazepam (7-ACT) is determined by the individual's acetylator phenotype.
- Pharmacogenetic variations influence the metabolic pathways of drugs like clonazepam.