Possible pharmacokinetic interaction with quinidine: ciprofloxacin or metronidazole?
OBJECTIVE
To discuss a potential pharmacokinetic interaction between quinidine, ciprofloxacin, and metronidazole.


METHODS
A 51-year-old black woman was admitted for shortness of breath, abdominal pain, and 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 quinidine concentration (SQC) on day 7 was 6.3 micrograms/mL (normal 2-5) with normal QT and QTc intervals. On day 8, the patient was discharged in normal sinus rhythm. She took her last doses of antibiotics on day 15 and a follow-up SQC on day 18 was 2.3 micrograms/mL.


CONCLUSIONS
The possible explanations 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 the elevated SQC and the patient had her prescriptions refilled within appropriate time limits. The third explanation seems more plausible. Quinidine is metabolized by the hepatic mixed-function oxidase system, specifically cytochrome P450 (CYP) 3A4. We found that metronidazole has been shown to inhibit CYP3A activity and ciprofloxacin has been shown to inhibit certain isozymes in the cytochrome P450 system as well.


CONCLUSIONS
When metronidazole and ciprofloxacin are administered concomitantly with quinidine, clinicians should be aware of this potential interaction. Quinidine concentrations should be monitored and patients should be assessed for signs and symptoms of quinidine toxicity.
Cooke
C E
CE
Medical University of South Carolina, Charleston, USA.
Sklar
G E
GE
Nappi
J M
JM
D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D000994:Antitrichomonal Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D002939:Ciprofloxacin / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008795:Metronidazole / Q000009:adverse effects / Q000493:pharmacokinetics*; D008875:Middle Aged; D011802:Quinidine / Q000009:adverse effects / Q000493:pharmacokinetics*
D000889:Anti-Arrhythmia Agents; D000890:Anti-Infective Agents; D000994:Antitrichomonal Agents; D008795:Metronidazole; D002939:Ciprofloxacin; D011802:Quinidine