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Reduced verapamil clearance during long-term oral administration
Clinical Pharmacology and Therapeutics
|November 1, 1981
Summary
Verapamil accumulates more than expected in patients with supraventricular tachycardia. This drug accumulation is linked to a longer verapamil half-life and reduced liver clearance over time.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Drug Metabolism
Background:
- Supraventricular tachycardia (SVT) is a common cardiac arrhythmia.
- Verapamil is a frequently prescribed calcium channel blocker for SVT management.
- Understanding verapamil pharmacokinetics is crucial for optimizing SVT treatment.
Purpose of the Study:
- To investigate the pharmacokinetic profile of verapamil and its metabolite, norverapamil, in SVT patients.
- To assess drug accumulation and changes in half-life (t1/2) during initial dosing.
- To determine the impact of repeated dosing on verapamil plasma concentrations.
Main Methods:
- Plasma concentrations of verapamil and norverapamil were measured in six SVT patients.
- Measurements were taken after the first and seventh doses of 120 mg verapamil every 8 hours.
- Area under the concentration-time curve (AUC) and half-life (t1/2) were calculated.
Main Results:
- Verapamil steady state was achieved by the seventh dose.
- Area under the concentration-time curve (AUC) at steady state was significantly higher than after the first dose (1999 vs. 788 ng/ml·hr, P < 0.001).
- Verapamil half-life (t1/2) prolonged from 2.75 hr to 4.52 hr, and norverapamil AUC also increased.
Conclusions:
- Verapamil exhibits greater-than-predicted accumulation in SVT patients.
- Reduced hepatic clearance contributes to verapamil accumulation and prolonged half-life.
- These findings highlight the importance of monitoring verapamil levels in SVT treatment.