The effect of coadministration of verapamil on the pharmacokinetics and metabolism of quinidine

We have previously found that verapamil pretreatment significantly inhibits the metabolism of antipyrine. To assess more fully the implications of this observation, we examined the effect of verapamil on the pharmacokinetics and metabolism of quinidine. Pretreatment with verapamil, 80 mg and 120 mg (every 8 hours for 3 days), reduced the oral clearance of quinidine from 17.0 L/hr to 11.6 and 11.3 L/hr, respectively (P less than 0.01). The half-life of quinidine was also significantly prolonged by verapamil. The formation clearance of 3-hydroxyquinidine was reduced by 61.2% and 70.6% after verapamil pretreatment (80 and 120 mg, respectively) (P less than 0.01), whereas the renal clearance of unchanged quinidine was not affected. These results indicate that verapamil impairs the metabolism of quinidine to 3-hydroxyquinidine and reduces the oral clearance of quinidine to a degree that could be of clinical significance given the narrow therapeutic index of this drug.