Analysis of different i.v. formulations of four medications prepared in syringes by anesthesiologists revealed a high rate of discrepancies between ordered and actual drug concentrations, suggesting a need for increased institutional efforts to prevent errors during the preparation process.
Background: There is some evidence that dextromethorphan (DM) is effective as a preemptive analgesic agent. DM is mainly metabolized to dextrorphan (DOR) by CYP2D6 whose
activity can be inhibited by pharmacologic intervention.
Objectives: To investigate the efficacy of DM as a pre-emptive analgesic agent and describe
the population pharmacokinetics in the presence of normal and poor CYP2D6 metabolism
in acute post-operative pain.
Study Design: Double blind, randomized, placebo-controlled trial
Setting: Post-surgical analgesic consumption after knee ligament surgery, a setting of acute
pain.
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: CYP2D6 inhibition by quinidine influenced the pre-emptive analgesic
effectiveness of DM confirming that CYP2D6 phenotypic switch increases the neuromodulatory
effect of oral dextromethorphan.
Key words: Pre-emptive analgesia, dextomethorphan, population kinetics, quinidine,
cytochrome 2D6
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.