Pharmacokinetic and pharmacodynamic interactions between diltiazem and quinidine.
OBJECTIVE
To examine the pharmacokinetic and pharmacodynamic interactions between quinidine and diltiazem because both drugs can inhibit drug 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 of 100 mg quinidine twice a day or 90 mg sustained-release diltiazem twice a day for 2 day 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 increased its terminal elimination half-life (t1/2) 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 significantly affected. Diltiazem disposition was not significantly affected by pretreatment with quinidine. Diltiazem pretreatment increased QTc and PR intervals and decreased heart rate and diastolic blood pressure. No significant pharmacodynamic differences were shown for diltiazem alone versus quinidine pretreatment.


CONCLUSIONS
Diltiazem significantly decreased the clearance and increased the t1/2 of quinidine, but quinidine did not alter the kinetics of diltiazem with the dose used. No significant pharmacodynamic interaction was shown for the combination that would not be predicted from individual drug administration.
Laganière
S
S
Bureau of Drug Research, Health Protection Branch, Health Canada, Ottawa, Ontario, Canada.
Davies
R F
RF
Carignan
G
G
Foris
K
K
Goernert
L
L
Carrier
K
K
Pereira
C
C
McGilveray
I
I
D000328:Adult; D000704:Analysis of Variance; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004110:Diltiazem / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D008297:Male; D011802:Quinidine / Q000493:pharmacokinetics / Q000494:pharmacology*; D012016:Reference Values; D013997:Time Factors; D014665:Vasodilator Agents / Q000493:pharmacokinetics / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D004110:Diltiazem; D011802:Quinidine