Vasquez E, Pollak R, Benedetti E
Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA.
Clin Transplant. 2001 Apr;15(2):95-9. doi: 10.1034/j.1399-0012.2001.150203.x.
In order to substantiate a previous case report of a drug interaction between tacrolimus and clotrimazole, we randomly assigned tacrolimus-treated renal allograft recipients to therapy with either clotrimazole or nystatin for oral thrush prophylaxis immediately following transplantation. Patients receiving other agents known to interact with cytochrome P450 were excluded from the study. The clotrimazole group consisted of 17 patients and the nystatin group, which served as the control group, consisted of 18 patients. An oral loading dose (approximately 0.3 mg/kg) of tacrolimus was given pre-operatively. Post-transplant, tacrolimus (approximately 0.15 mg/kg) was orally administered twice daily. Clotrimazole therapy consisted of a 10-mg troche administered three times daily. Nystatin therapy consisted of the oral suspension (5 mL) administered as a 'swish and swallow' four times daily. We evaluated tacrolimus trough blood levels and tacrolimus doses on days 1, 3, 5, and 7 following transplantation. On post-transplant day 1, mean tacrolimus trough levels did not differ between clotrimazole- and nystatin-treated patients. Mean tacrolimus blood trough levels were significantly higher in clotrimazole-treated patients on days 3, 5, and 7 post-transplant, 42+/-14, 53+/-7, and 33+/-17 ng/mL, respectively, compared to 15+/-8, 15+/-7, and 14+/-6 ng/mL in nystatin-treated patients (p<0.05). The mean tacrolimus dose was significantly lower in the clotrimazole group by day 7 post-transplant (p<0.05). We conclude that clotrimazole therapy may cause a significant rise in tacrolimus trough blood levels. Recognition of this potential drug interaction is essential to minimize tacrolimus-associated toxicities in the early post-transplant period.
为了证实之前一份关于他克莫司与克霉唑药物相互作用的病例报告，我们将接受他克莫司治疗的肾移植受者在移植后立即随机分为两组，一组接受克霉唑治疗，另一组接受制霉菌素治疗，用于预防口腔念珠菌病。接受其他已知与细胞色素P450相互作用药物治疗的患者被排除在研究之外。克霉唑组由17例患者组成，制霉菌素组作为对照组，由18例患者组成。术前给予他克莫司口服负荷剂量（约0.3mg/kg）。移植后，他克莫司（约0.15mg/kg）每日口服两次。克霉唑治疗方案为每日三次含服10mg含片。制霉菌素治疗方案为每日四次口服混悬液（5mL），采用“含漱后咽下”的方式。我们在移植后第1、3、5和7天评估了他克莫司的血药谷浓度和他克莫司剂量。移植后第1天，接受克霉唑和制霉菌素治疗的患者的他克莫司血药谷浓度无差异。移植后第3、5和7天，接受克霉唑治疗的患者的他克莫司血药谷浓度显著更高，分别为42±14、53±7和33±17ng/mL，而接受制霉菌素治疗的患者分别为15±8、15±7和14±6ng/mL（p<0.05）。移植后第7天，克霉唑组的他克莫司平均剂量显著更低（p<0.05）。我们得出结论，克霉唑治疗可能导致他克莫司血药谷浓度显著升高。认识到这种潜在的药物相互作用对于在移植后早期将他克莫司相关毒性降至最低至关重要。
