Katayama Masaaki, Igarashi Hiroyuki, Tani Kenji, Nezu Yoshinori, Harada Yasuji, Yogo Takuya, Hara Yasushi, Aoki Shinobu, Tagawa Masahiro
Department of Veterinary Medicine, Faculty of Agriculture, Iwate University, Iwate, Japan.
J Vet Med Sci. 2008 Jan;70(1):85-8. doi: 10.1292/jvms.70.85.
Fluconazole (Fcz) is successfully used in human organ transplant patients as an antifungal therapy. However, Fcz can increase the cyclosporine (CsA) trough level and lead to CsA nephrotoxicity. In canine renal transplantation, CsA has been used as a major immunosuppressant, and it is important to control its trough level. However, the interaction of Fcz with CsA has not yet been reported in dogs. In this study, the effect of Fcz treatment on the pharmacokinetics of CsA in four healthy beagles was investigated using a four-period crossover design. The treatments included CsA alone (A), CsA + multiple-dose Fcz 50 mg (B), CsA + multiple-dose Fcz 25 mg (C) and CsA + single-dose Fcz 50 mg (D). Blood CsA concentrations were measured at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hr after CsA administration. The AUC(0-12) and C(max) values for treatment B were significantly higher than those for the other treatments. In particular, the AUC(0-12) of treatment B was about two times higher than that of treatment A. Fcz administration did not significantly prolong the half-life or mean residence time of CsA. The results of our study show that administration of multiple therapeutic doses of Fcz can significantly increase the CsA blood concentration, which might partially depend upon the Fcz blood concentration. When Fcz is used in CsA-based canine renal transplantation, it may be necessary to adjust the CsA trough level by decreasing the dose.
氟康唑（Fcz）已成功用于人体器官移植患者的抗真菌治疗。然而，Fcz可提高环孢素（CsA）的谷浓度并导致CsA肾毒性。在犬肾移植中，CsA一直被用作主要的免疫抑制剂，控制其谷浓度很重要。然而，Fcz与CsA在犬类中的相互作用尚未见报道。本研究采用四周期交叉设计，研究了Fcz治疗对4只健康比格犬体内CsA药代动力学的影响。治疗方案包括单独使用CsA（A）、CsA + 多剂量50 mg Fcz（B）、CsA + 多剂量25 mg Fcz（C）和CsA + 单剂量50 mg Fcz（D）。在给予CsA后0.5、1、2、4、6、8、10、12和24小时测量血液中CsA浓度。治疗B的AUC(0 - 12)和C(max)值显著高于其他治疗组。特别是，治疗B的AUC(0 - 12)约为治疗A的两倍。给予Fcz并未显著延长CsA的半衰期或平均驻留时间。我们的研究结果表明，给予多治疗剂量的Fcz可显著提高CsA的血药浓度，这可能部分取决于Fcz的血药浓度。当Fcz用于基于CsA的犬肾移植时，可能需要通过降低剂量来调整CsA的谷浓度。
