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Novel single-point plasma or saliva dextromethorphan method for determining CYP2D6 activity
1Pharmaceutical Research Institute and School of Pharmacy, Taipei and Laboratory of Biological Psychiatry, Taipei City Psychiatric Center, Taipei, Taiwan, Republic of China.
Summary
This study validates new methods for CYP2D6 phenotyping using dextromethorphan (DXM) metabolic ratios. Plasma or saliva samples collected at specific times offer reliable and repeatable DXM phenotyping, improving upon traditional urine-based methods.
Area of Science:
- Pharmacogenomics
- Drug Metabolism
- Clinical Chemistry
Background:
- CYP2D6 phenotyping is crucial for personalized medicine.
- O-demethylation of dextromethorphan (DXM) is a common CYP2D6 probe.
- Traditional 8-hour urine collection for DXM metabolic ratio (MR) is cumbersome.
Purpose of the Study:
- To evaluate the repeatability and validity of DXM MR for CYP2D6 phenotyping.
- To compare DXM MR from urine, plasma, and saliva samples.
- To assess DXM MR after single and multiple DXM doses.
Main Methods:
- 12 subjects received single 15 mg DXM doses; 16 subjects received multiple 60 mg controlled-release DXM doses.
- Urine, plasma, and saliva samples were collected at various time points.
- DXM and dextrorphan levels were quantified using high-performance liquid chromatography (HPLC).
Main Results:
- DXM MR from urine (4-12h), plasma (1-5h, 8h), and saliva (2h, 6h) after single doses correlated with 24h urine/AUC.
- Plasma (0.5-10h) and saliva (3-12h) DXM MR after multiple doses predicted AUC.
- Single-dose plasma (2-5h) and saliva (6h) MR significantly correlated with multiple-dose MR (r > 0.8).
Conclusions:
- Plasma sampling at 2-5 hours or saliva sampling at 6 hours is suitable for DXM MR determination.
- These methods offer repeatable and valid CYP2D6 phenotyping.
- DXM MR analysis using plasma or saliva improves upon traditional urine-based methods.