Nicolau D P, Crowe H M, Nightingale C H, Quintiliani R
Division of Infectious Disease, Hartford Hospital, CT 06102, USA.
Ann Pharmacother. 1995 Oct;29(10):994-6. doi: 10.1177/106002809502901007.
To report the influence of rifampin coadministration on the pharmacokinetics of fluconazole in 2 critically ill patients.
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.
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.
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.
报告利福平联合用药对2例重症患者氟康唑药代动力学的影响。
报告了重症监护病房（ICU）5例患者的氟康唑药代动力学情况，其中2例接受利福平治疗，3例仅接受氟康唑治疗。患者1为一名52岁男性，患有双侧肺炎，因怀疑真菌二重感染加用氟康唑时，除其他抗生素外还接受了9天的利福平治疗。患者2为一名39岁男性，患有激素依赖性哮喘，因右中叶肺炎和通气功能不全入住ICU。由于临床病情迅速恶化，在常规抗菌治疗基础上加用静脉注射利福平600mg，每12小时1次，氟康唑100mg，每24小时1次。患者3 - 5接受静脉氟康唑治疗，但在抗真菌治疗前从未使用过利福平。
氟康唑因其疗效、低毒性以及报道的药物相互作用较少而被广泛用作抗真菌药物。然而，在某些临床情况下，该药物必须与利福平联合使用。健康志愿者的有限数据表明，利福平与氟康唑联合使用会使氟康唑浓度 - 时间曲线下面积（AUC）降低23%。在本报告中，我们发现接受利福平治疗的患者中，氟康唑的AUC有统计学意义的降低（52%），全身清除率提高了93%。
虽然描述氟康唑与利福平在患者中相互作用程度的数据有限，但我们的数据表明这种相互作用比先前报道的更为显著。如果不可避免地同时使用这两种药物，应密切监测患者的临床治疗反应，因为氟康唑血清浓度意外大幅降低可能导致治疗效果不佳。
