Abstract | BACKGROUND: There is some evidence that dextromethorphan (DM) is effective as a pre-emptive analgesic agent. DM is mainly metabolized to dextrorphan (DOR) by CYP2D6 whose activity can be inhibited by pharmacologic intervention. OBJECTIVES: STUDY DESIGN: Double blind, randomized, placebo-controlled trial SETTING: METHODS: Forty patients were randomized to a single oral dose of 50 mg quinidine or placebo, administered 12 hours before 50 mg DM. Patients were genotyped for the major CYP2D6 and ABCB1 variants and phenotyped for CYP2D6 using urine DM/DOR metabolic ratios and blood samples for population pharmacokinetic modeling. RESULTS:
Quinidine was effective in inhibiting CYP2D6 activity, with 2-fold reduction of DM to DOR biotransformation clearance, prolonged DM half-life, and increased DM systemic availability. Patients in the quinidine group required significantly less often NSAIDs than patients in the placebo group (35.3% vs. 75.0%, P = 0.022). The odds ratio for NSAID consumption in the placebo vs. quinidine group was 5.5 (95% confidence interval (CI) 1.3 - 22.7) at 48 hours after surgery. LIMITATIONS: While this study shows an impact of DM on pre-emptive analgesia and is mechanistically interesting, the findings need to be confirmed in larger trials. CONCLUSION:
|
Authors | Georg B Ehret, Youssef Daali, Jocelyne Chabert, Michela Rebsamen, Adriana Wolff, Alain Forster, Fouzia Moursli, Daniel Fritschy, Michel F Rossier, Valérie Piguet, Pierre Dayer, Marianne Gex-Fabry, Jules A Desmeules |
Journal | Pain physician
(Pain Physician)
Vol. 16
Issue 1
Pg. 45-56
(Jan 2013)
ISSN: 2150-1149 [Electronic] United States |
PMID | 23340533
(Publication Type: Journal Article, Randomized Controlled Trial)
|
Chemical References |
- Adrenergic alpha-Antagonists
- Anti-Inflammatory Agents, Non-Steroidal
- Excitatory Amino Acid Antagonists
- N-Methylaspartate
- Dextromethorphan
- Cytochrome P-450 CYP2D6
- Quinidine
|
Topics |
- Adolescent
- Adrenergic alpha-Antagonists
(pharmacology)
- Adult
- Analgesia
(methods)
- Anti-Inflammatory Agents, Non-Steroidal
(therapeutic use)
- Cytochrome P-450 CYP2D6
(genetics, metabolism)
- Dextromethorphan
(therapeutic use)
- Double-Blind Method
- Excitatory Amino Acid Antagonists
(therapeutic use)
- Female
- Genotype
- Humans
- Male
- Middle Aged
- N-Methylaspartate
- Pain Measurement
- Pain, Postoperative
(genetics, metabolism, prevention & control)
- Quinidine
(pharmacology)
- Young Adult
|