The effect of ciprofloxacin on the pharmacokinetic and ECG parameters of quinidine.
Ciprofloxacin decreases the clearance of antipyrine and other drugs which, in part, undergo oxidative metabolism. Based on these findings, the authors hypothesized that ciprofloxacin may decrease the clearance of quinidine, a drug which also undergoes oxidative metabolism. The purpose of this study was to evaluate the effect of ciprofloxacin on the pharmacokinetic and ECG parameters of quinidine in seven healthy men. Oral quinidine sulfate 400 mg was administered alone (Phase A) and after oral ciprofloxacin pretreatment (Phase B) in a randomized crossover fashion with a 2-week washout period between each phase. During Phase B, ciprofloxacin pretreatment (750 mg every 12 hours) was administered for 5 days before and 24 hours after quinidine administration. Quinidine serum samples were obtained over a 24-hour period. QRS and QTc intervals were measured over a 12-hour period. There were no significant differences in clearance (20.3 +/- 3.3 L/hr vs 20.1 +/- 2.3 L/hr, P = .836), half-life (7.9 +/- 1 hr vs 7.8 +/- 0.8 hr, P = 0.8), maximum concentration (1.4 +/- 0.6 mg/L vs 1.5 +/- 0.6 mg/L, P = 0.613), or time to maximum concentration (1.5 +/- 0.2 hr vs 1.5 +/- 0.1 hr, P = 0.571) for quinidine between Phase A and Phase B, respectively. The largest decrease in clearance observed for Phase B compared to Phase A was 10%. There was also no significant difference in the degree of QRS and QTc prolongation between Phase A and Phase B. From these results, it appears that ciprofloxacin in the dose given does not alter the pharmacokinetic or ECG parameters of quinidine. Therefore, no adjustment in the dose of quinidine is needed when coadministered with ciprofloxacin.
Bleske
B E
BE
University of Michigan, College of Pharmacy, Ann Arbor 48109-1065.
Carver
P L
PL
Annesley
T M
TM
Bleske
J R
JR
Morady
F
F
D000328:Adult; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D008297:Male; D011802:Quinidine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D011897:Random Allocation; D013997:Time Factors
D002939:Ciprofloxacin; D011802:Quinidine