Dowell James A, Stogniew Martin, Krause David, Henkel Timothy, Damle Bharat
Clinical Pharmacology, Pfizer Global Research & Development, 685 3rd Avenue, New York, NY 10017, USA.
J Clin Pharmacol. 2007 Mar;47(3):305-14. doi: 10.1177/0091270006296764.
The safety and pharmacokinetics of anidulafungin coadministered with tacrolimus were investigated using a single-sequence, open-label design. Healthy volunteers received 5 mg tacrolimus orally on days 1 and 13 of the study. Anidulafungin (200 mg) was administered intravenously on day 4, followed by 100-mg doses on days 5 through 13. Key pharmacokinetic parameters, including C(max), AUC, t((1/2)), CL, and V(ss), were derived from concentration-time data. The 90% confidence intervals (CIs) of the ratios of mean pharmacokinetic parameters of anidulafungin plus tacrolimus to each drug alone were well within the 80% to 125% bioequivalence range, indicating no pharmacokinetic interaction. This ratio was 101.6 (90% CI: 92.77-111.22) for tacrolimus AUC(0-infinity) and 107.2 (90% CI: 105.1-109.4) for anidulafungin AUC(ss). The 2 drugs were well tolerated, and no drug-related serious adverse events were reported. Because of its lack of pharmacokinetic interaction with key immunosuppressive agents, anidulafungin is an important option for the prevention and treatment of invasive fungal infections in transplant recipients.
采用单序列、开放标签设计研究了阿尼芬净与他克莫司联合使用时的安全性和药代动力学。健康志愿者在研究的第1天和第13天口服5mg他克莫司。在第4天静脉注射阿尼芬净（200mg），随后在第5天至第13天每天注射100mg剂量。关键药代动力学参数，包括C(max)、AUC、t((1/2))、CL和V(ss)，由浓度-时间数据得出。阿尼芬净加他克莫司的平均药代动力学参数与每种药物单独使用时的平均药代动力学参数之比的90%置信区间（CI）完全在80%至125%的生物等效性范围内，表明不存在药代动力学相互作用。他克莫司AUC(0-无穷大)的该比值为101.6（90%CI：92.77-111.22），阿尼芬净AUC(稳态)的该比值为107.2（90%CI：105.1-109.4）。这两种药物耐受性良好，未报告与药物相关的严重不良事件。由于阿尼芬净与关键免疫抑制剂缺乏药代动力学相互作用，它是预防和治疗移植受者侵袭性真菌感染的重要选择。
