Shirai Sayuri, Yasuda Takashi, Tsuchida Hiroki, Kuboshima Shingo, Konno Yusuke, Shima Yoshinori, Sato Takeo, Hatta Shigeo, Masuhara Keisou, Kimura Kenjirou
Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.
Department of Pharmacy, St. Marianna University School of Medicine, Kawasaki, Japan.
Clin Exp Nephrol. 2009 Apr;13(2):123-129. doi: 10.1007/s10157-008-0112-z. Epub 2008 Dec 5.
BACKGROUND/AIMS: The present study evaluated the clinical efficacy and pharmacokinetics of microemulsion cyclosporine A (ME-CyA) with modification from postprandial to preprandial administration in adult patients with refractory nephrotic syndrome.
We investigated 19 patients with refractory nephrotic syndrome who had been switched from the postprandial administration of ME-CyA to preprandial administration. The pharmacokinetics of ME-CyA were also evaluated before and 6 months after switching from postprandial to preprandial administration by serial measurement of the blood CyA concentration in 10 patients.
This study showed that 16 of 19 patients (84%) displayed an improvement in their clinical condition or continued to maintain remission after switching from post- to preprandial administration. In particular among 14 patients with minimal change nephrotic syndrome (MCNS) in this study, 13 patients maintained or achieved remission under preprandial ME-CyA administration. Only three of 10 patients with postprandial administration showed a peak concentration> 500 ng/ml within 1-2 h after administration, while with preprandial administration, nine of 10 patients showed this good absorption profiles. This effectiveness of preprandial administration seems to be dependent on the improved pharmacokinetics with the increase of area under the curve from 0-4 h (AUC(0-4)) and peak concentration. There were no statistical differences in the mean daily doses of ME-CyA between both administration periods. No ME-CyA-induced nephrotoxicity or other harmful events were encountered throughout the study.
The preprandial administration of ME-CyA results in a good pharmacokinetic profile and is useful for management of refractory nephrotic syndrome in adults, particularly in patients with MCNS.
背景/目的：本研究评估了微乳环孢素A（ME-CyA）从餐后给药改为餐前给药在成年难治性肾病综合征患者中的临床疗效和药代动力学。
我们调查了19例从ME-CyA餐后给药改为餐前给药的难治性肾病综合征患者。通过连续测量10例患者的血环孢素A浓度，还评估了从餐后给药改为餐前给药前及给药6个月后的ME-CyA药代动力学。
本研究表明，19例患者中有16例（84%）在从餐后给药改为餐前给药后临床状况改善或持续维持缓解。特别是在本研究的14例微小病变肾病综合征（MCNS）患者中，13例在餐前ME-CyA给药下维持或实现缓解。餐后给药的10例患者中只有3例在给药后1-2小时内峰值浓度>500 ng/ml，而餐前给药时，10例患者中有9例呈现这种良好的吸收情况。餐前给药的这种有效性似乎取决于药代动力学的改善，0-4小时曲线下面积（AUC(0-4)）和峰值浓度增加。两个给药期之间ME-CyA的平均日剂量无统计学差异。在整个研究过程中未遇到ME-CyA引起的肾毒性或其他有害事件。
ME-CyA餐前给药导致良好的药代动力学特征，对成人难治性肾病综合征的管理有用，特别是对MCNS患者。
