氟伐他汀缓释片与环孢素在肾移植受者中的药代动力学相互作用评估。

Evaluation of the pharmacokinetic interaction between fluvastatin XL and cyclosporine in renal transplant recipients.

作者信息

Holdaas H, Hagen E, Asberg A, Lund K, Hartman A, Vaidyanathan S, Prasad P, He Y L, Yeh C M, Bigler H, Rouilly M, Denouel J

机构信息

Department of Medicine, National Hospital, Sognsvannsveien 20, 0027 Oslo, Norway.

出版信息

Int J Clin Pharmacol Ther. 2006 Apr;44(4):163-71. doi: 10.5414/cpp44163.

DOI:10.5414/cpp44163

PMID:16625985

Abstract

OBJECTIVE

To assess the pharmacokinetic interaction between cyclosporine and extended-release fluvastatin (fluvastatin XL), 80 mg for 7 days, in stable renal transplant recipients.

METHODS

This was a single-center, open-label study. 17 renal transplant recipients received their standard cyclosporine therapy (Days 1 - 9) plus a once-daily single oral dose of fluvastatin XL, 80 mg (Days 2 - 8). Blood samples were collected and cyclosporine (whole blood) and fluvastatin (plasma) concentrations determined by radioimmunoassay and HPLC fluorescence detection, respectively. Pharmacokinetic parameters were calculated using non-compartment analysis and fluvastatin results were compared with historical controls.

RESULTS

Treatment with fluvastatin XL, 80 mg for 7 days, had no significant effect on either the AUC0-12 (3,644 ng x h/ml in the absence of fluvastatin vs. 3,534 ng x h/ml in the presence of fluvastatin) or the Cmax of cyclosporine (983 ng/ml in the absence of fluvastatin vs. 945 ng/ml in the presence of fluvastatin). Co-administration of fluvastatin XL also had no effect on the tmax, t1/2 or apparent clearance (CL/F) of cyclosporine in renal transplant patients. The AUC and Cmax for fluvastatin XL in the presence of cyclosporine (AUC0-24 1,192 ng. x h/ml, Cmax 271 ng/ml) were approximately 2-fold higher compared with historical data for fluvastatin XL alone in healthy volunteers (AUC0-24 630 ng x h/ml, Cmax 102 ng/ml) but lower than the historical data for fluvastatin IR, 40 mg b.i.d. alone in healthy volunteers (AUC0-24 1,340 ng x h/ml, Cmax 443 ng/ml). Tmax, t1/2 and trough levels of fluvastatin in the presence of cyclosporine were also similar to the historical controls. Concomitant administration of cyclosporine and fluvastatin XL was well tolerated by renal transplant recipients.

CONCLUSIONS

Fluvastatin XL, 80 mg, and cyclosporine do not show clinically relevant pharmacokinetic interactions.

摘要

目的

评估在稳定的肾移植受者中，环孢素与80mg缓释氟伐他汀（氟伐他汀XL）连用7天的药代动力学相互作用。

方法

这是一项单中心、开放标签研究。17名肾移植受者接受标准环孢素治疗（第1 - 9天）加每日一次口服单剂量80mg氟伐他汀XL（第2 - 8天）。采集血样，分别通过放射免疫分析和高效液相色谱荧光检测法测定环孢素（全血）和氟伐他汀（血浆）浓度。使用非房室分析计算药代动力学参数，并将氟伐他汀的结果与历史对照进行比较。

结果

服用80mg氟伐他汀XL 7天，对环孢素的AUC0 - 12（未服用氟伐他汀时为3,644ng·h/ml，服用氟伐他汀时为3,534ng·h/ml）或Cmax（未服用氟伐他汀时为983ng/ml，服用氟伐他汀时为945ng/ml）均无显著影响。联用氟伐他汀XL对肾移植患者中环孢素的tmax、t1/2或表观清除率（CL/F）也无影响。与健康志愿者单独使用氟伐他汀XL的历史数据（AUC0 - 24 630ng·h/ml，Cmax 102ng/ml）相比，在环孢素存在的情况下，氟伐他汀XL的AUC和Cmax（AUC0 - 24 1,192ng·h/ml，Cmax 271ng/ml）大约高出2倍，但低于健康志愿者单独使用40mg bid氟伐他汀IR的历史数据（AUC0 - 24 1,340ng·h/ml，Cmax 443ng/ml）。环孢素存在时氟伐他汀的tmax、t1/2和谷浓度也与历史对照相似。肾移植受者对环孢素和氟伐他汀XL的联用耐受性良好。