PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTIONS BETWEEN DILTIAZEM AND QUINIDINE

Objectives: To examine the pharmacokinetic and pharmacodynamic interac tions between quinidine and diltiazem because both drugs can inhibit d rug metabolism, Methods: Twelve fasting, healthy male volunteers (age, 24 +/- 5 years; weight, 75 +/- 10 kg) received a single oral dose of diltiazem (60 mg) or quinidine (200 mg), alone and on a background of the other drug, in a crossover study, Background treatment consisted o f 100 mg quinidine twice a day or 90 mg sustained-release diltiazem tw ice a day for 2 days before the study day, Results: Pretreatment with diltiazem significantly (p < 0.05) increased the area under the curve of quinidine from 7414 +/- 1965 to 11,213 +/- 2610 ng . hr/ml and incr eased its terminal elimination half-life (t(1/2)) from 6.8 +/- 1.1 to 9.3 +/- 1.5 hours, Its oral clearance was decreased from 0.39 +/- 0.1 to 0.25 +/- 0.1 L/hr/kg, whereas the maximal concentration was not sig nificantly affected. Diltiazem disposition was not significantly affec ted by pretreatment with quinidine. Diltiazem pretreatment increased Q T(c) and PR intervals and decreased heart rate and diastolic blood pre ssure, No significant pharmacodynamic differences were shown for dilti azem alone versus quinidine pretreatment, Conclusion: Diltiazem signif icantly decreased the clearance and increased the t(1/2) of quinidine, but quinidine did not alter the kinetics of diltiazem with the dose u sed, No significant pharmacodynamic interaction was shown for the comb ination that would not be predicted from individual drug administratio n.