Schroeder T J, Cho M J, Pollack G M, Floc'h R, Moran H B, Levy R, Moore L W, Pouletty P
SangStat Medical Corporation, Menlo Park, California 94025, USA.
J Clin Pharmacol. 1998 Sep;38(9):807-14.
This study was conducted to establish bioequivalence between a newly developed oral cyclosporine formulation, Sang-35 (SangStat Medical Corp., Menlo Park, CA), and the microemulsion formulation Neoral (Novartis Pharmaceuticals, East Hanover, NJ). In a randomized, open-label, two-way crossover study, 36 fasted, healthy male volunteers received a single 500-mg cyclosporine dose formulated either as Sang-35 or Neoral. Mean are under the concentration-time curve to infinity (AUC0-infinity) for Sang-35 was 13,900 microg x hr/L compared with 14,000 microg x hr/L for Neoral, with a 90% confidence interval (CI) of 96% to 103% for the geometric mean ratio of the two formulations. Mean maximum concentration (Cmax) was 1,690 microg/L for Sang-35 and 1,700 microg/L for Neoral, with a 90% CI of 96% to 103%. Geometric mean ratios for both AUC0-infinity and Cmax were within the acceptance criteria for bioequivalence (80-125%). Additional studies showed no differences between Sang-35 and Neoral after high-fat meals (n = 19), in female volunteers (n = 25) and in black volunteers (n = 7). It is concluded that single doses of the oral cyclosporine formulations Sang-35 and Neoral are bioequivalent in healthy fasted subjects, after high-fat meals, in women, and in blacks.
本研究旨在确定新开发的口服环孢素制剂Sang - 35（SangStat Medical Corp.，加利福尼亚州门洛帕克）与微乳剂制剂Neoral（诺华制药公司，新泽西州东哈嫩）之间的生物等效性。在一项随机、开放标签、双向交叉研究中，36名空腹健康男性志愿者接受了单次500毫克以Sang - 35或Neoral形式配制的环孢素剂量。Sang - 35的浓度 - 时间曲线下面积至无穷大（AUC0 - ∞）均值为13,900μg·hr/L，而Neoral为14,000μg·hr/L，两种制剂几何平均比的90%置信区间（CI）为96%至103%。Sang - 35的平均最大浓度（Cmax）为1,690μg/L，Neoral为1,700μg/L，90% CI为96%至103%。AUC0 - ∞和Cmax的几何平均比均在生物等效性的接受标准（80 - 125%）范围内。其他研究表明，高脂餐后（n = 19）、女性志愿者（n = 25）和黑人志愿者（n = 7）中，Sang - 35和Neoral之间无差异。结论是，口服环孢素制剂Sang - 35和Neoral的单剂量在健康空腹受试者、高脂餐后、女性和黑人中具有生物等效性。
