POSSIBLE PHARMACOKINETIC INTERACTION WITH QUINIDINE - CIPROFLOXACIN OR METRONIDAZOLE

OBJECTIVE: To discuss a potential pharmacokinetic interaction between quinidine, ciprofloxacin, and metronidazole. CASE SUMMARY: A 51-year-o ld black woman was admitted for shortness of breath, abdominal pain, a nd atrial fibrillation. Procainamide and diltiazem were begun for the atrial fibrillation and ciprofloxacin and metronidazole for suspected diverticulitis. The therapy was switched to quinidine on day 5 because of adverse events associated with procainamide. A trough serum quinid ine concentration (SQC) on day 7 was 6.3 mu g/mL (normal 2-5) with nor mal QT and QTc intervals. On day 8, the patient was discharged in norm al sinus rhythm. She took her last doses of antibiotics on day 15 and a follow-up SQC on day 18 was 2.3 mu g/mL. DISCUSSION: The possible ex planations for the changes in SQCs include: (1) laboratory error, (2) compliance with medication regimen, and (3) altered hepatic metabolism . The first two are not likely in this case. The laboratory verified t he elevated SQC and the patient had her prescriptions refilled within appropriate time limits. The third explanation seems more plausible. Q uinidine is metabolized by the hepatic mixed-function oxidase system, specifically cytochrome P450 (CYP) 3A4. We found that metronidazole ha s been shown to inhibit CYP3A activity and ciprofloxacin has been show n to inhibit certain isozymes in the cytochrome P450 system as well. C ONCLUSIONS: When metronidazole and ciprofloxacin are administered conc omitantly with quinidine, clinicians should be aware of this potential interaction. Quinidine concentrations should be monitored and patient s should be assessed for signs and symptoms of quinidine toxicity.