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Enhanced metabolism and diminished efficacy of disopyramide by enzyme induction?
Abstract:
1 Monitoring plasma levels of mono-N-dealkyldisopyramide (MND), the most important metabolite of disopyramide, has been considered unnecessary. 2 We measured plasma levels of both disopyramide and MND in 64 consecutive patients receiving long term oral therapy with disopyramide. 3 Six patients were found with high plasma levels of MND, and simultaneously low levels of disopyramide. 4 Three of these patients were taking simultaneously phenytoin. The other three had a relatively high dose of disopyramide with regard to their renal function. One patient had terminal uremia, three had less severe renal dysfunction. 5 The underlying mechanism and clinical significance of the findings are discussed.
Insights
Monitoring mono-N-dealkyldisopyramide (MND) levels is crucial for patients on disopyramide therapy. High MND with low disopyramide levels were observed in some patients, indicating potential therapeutic drug monitoring needs.
Area of Science:
- Clinical Pharmacology
- Pharmacokinetics
- Drug Metabolism
Background:
- Disopyramide is an antiarrhythmic drug.
- Mono-N-dealkyldisopyramide (MND) is the primary metabolite of disopyramide.
- Monitoring MND plasma levels has been considered unnecessary.
Purpose of the Study:
- To investigate the necessity of monitoring MND plasma levels.
- To assess the relationship between disopyramide and MND levels in patients on long-term therapy.
Main Methods:
- Plasma levels of disopyramide and MND were measured.
- 64 patients receiving long-term oral disopyramide therapy were included.
- Patient data included concurrent medications and renal function.
Main Results:
- Six patients exhibited high MND and low disopyramide plasma levels.
- Three of these patients were co-administered phenytoin.
- Other patients with high MND levels had high disopyramide doses relative to renal function, including those with renal dysfunction.
Conclusions:
- High MND levels may indicate altered disopyramide metabolism or elimination.
- Phenytoin co-administration and renal dysfunction are potential factors influencing MND levels.
- Routine monitoring of MND may be warranted in specific patient populations.