Rifampin-fluconazole interaction in critically ill patients.
OBJECTIVE
To report the influence of rifampin coadministration on the pharmacokinetics of fluconazole in 2 critically ill patients.


METHODS
The pharmacokinetics of fluconazole are reported in 5 patients in the intensive care unit (ICU), 2 of whom received rifampin and 3 who received only fluconazole. Patient 1 was a 52 year-old man with bilateral pneumonia who received rifampin for 9 days in addition to other antibiotics when fluconazole was added for suspected fungal superinfection. Patient 2, a 39-year-old man with steroid-dependent asthma was admitted to the ICU with a right middle lobe pneumonia and ventilatory insufficiency. Because of rapid clinical deterioration, intravenous rifampin 600 mg q12h and fluconazole 100 mg q24h were added to conventional antibacterial therapy. Patients 3-5 received intravenous fluconazole therapy, but were never administered rifampin prior to their antifungal therapy.


CONCLUSIONS
Fluconazole has gained wide use as an antifungal agent because of its efficacy, limited toxicity, and the paucity of reported drug interactions. In some clinical situations, however, the drug must be coadministered with rifampin. Limited data in healthy volunteers suggest that the coadministration of rifampin and fluconazole results in a 23% reduction in the fluconazole area under the concentration-time curve (AUC). In this report, we found a statistically significant lowering of the AUC (52%) and a 93% higher total body clearance of fluconazole in patients treated with rifampin.


CONCLUSIONS
Although limited data are available describing the magnitude of the interaction between fluconazole and rifampin in patients, our data suggest a more significant interaction than previously reported. If the concurrent administration of the 2 drugs in unavoidable, the patient's clinical response to treatment should be monitored closely, as the unexpectedly large reduction in fluconazole serum concentrations may lead to poor treatment outcomes.
Nicolau
D P
DP
Division of Infectious Disease, Hartford Hospital, CT 06102, USA.
Crowe
H M
HM
Nightingale
C H
CH
Quintiliani
R
R
D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D016638:Critical Illness; D004347:Drug Interactions; D015725:Fluconazole / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D012293:Rifampin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D015725:Fluconazole; D012293:Rifampin