Min D I, Hwang G C, Bergstrom S, Madras P N, Shaffer D, Sahyoun A I, Monaco A P
Department of Pharmacy Practice, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, MA 02115.
Ann Pharmacother. 1992 Feb;26(2):175-9. doi: 10.1177/106002809202600205.
To evaluate the relative bioavailability and patient acceptance of cyclosporine (CSA) soft gelatin capsule versus oral solution in renal allograft recipients.
DESIGN, SETTING, AND PATIENTS: The bioavailability of CSA capsules was compared with that of CSA solution with crossover study design in the outpatient clinic setting. Nine renal allograft recipients with stable renal function participated in this study.
CSA dose was switched from solution to capsule in each patient for seven days. At steady-state, nine blood samples were obtained over a 12-hour period from each patient on day 7 for CSA solution and on day 14 for CSA capsules. CSA blood samples were analyzed by HPLC and fluorescence polarization immunoassay (FPIA) methods. Time to peak concentration (Tmax), peak concentration (Cmax), and area under the curve (AUC) were calculated on days 7 and 14, and compared using the matched Student's t-test. Patient acceptance was evaluated by patient preference on the questionnaire.
For CSA blood concentrations measured by HPLC assay, the Tmax, Cmax, and AUC were 3.4 +/- 1.3 h, 569 +/- 240 nmol/L, and 4659 +/- 2144 h.nmol/L (mean +/- SD), respectively, with solution and 4.2 +/- 2.1 h, 560 +/- 257 nmol/L, and 4765 +/- 1799 h.nmol/L (mean +/- SD), respectively, with capsules. These differences were not significant (p greater than 0.1). The bioavailability was not significantly different between capsules and solutions when it was measured by PFIA assay (p greater than 0.1). The mean (+/- SD) relative bioavailability of capsules compared with solution was 109 +/- 29 percent AUC (0-12 h) measured by HPLC and 111 +/- 27 percent AUC (0-12 h) measured by FPIA. All patients expressed preference for capsules over the solution.
CSA oral soft gelatin capsule is bioequivalent to CSA oral solution and most patients preferred the capsule to the oral solution.
评估肾移植受者中环孢素（CSA）软胶囊与口服溶液的相对生物利用度及患者接受度。
设计、地点和患者：采用交叉研究设计在门诊环境中比较CSA胶囊与CSA溶液的生物利用度。9名肾功能稳定的肾移植受者参与了本研究。
每位患者的CSA剂量从溶液转换为胶囊，持续7天。在稳态时，于第7天对每位患者在12小时内采集9份血样用于CSA溶液检测，于第14天采集用于CSA胶囊检测。CSA血样采用高效液相色谱法（HPLC）和荧光偏振免疫分析法（FPIA）进行分析。计算第7天和第14天的达峰时间（Tmax）、峰浓度（Cmax）和曲线下面积（AUC），并使用配对学生t检验进行比较。通过问卷中患者的偏好来评估患者接受度。
对于通过HPLC法测定的CSA血药浓度，溶液组的Tmax、Cmax和AUC分别为3.4±1.3小时、569±240纳摩尔/升和4659±2144小时·纳摩尔/升（均值±标准差），胶囊组分别为4.2±2.1小时、560±257纳摩尔/升和4765±1799小时·纳摩尔/升（均值±标准差）。这些差异无统计学意义（p＞0.1）。通过PFIA法测定时，胶囊与溶液之间的生物利用度无显著差异（p＞0.1）。与溶液相比，胶囊的平均（±标准差）相对生物利用度通过HPLC测定的AUC（0 - 12小时）为109±29%，通过FPIA测定的AUC（0 - 12小时）为111±27%。所有患者均表示更喜欢胶囊而非溶液。
CSA口服软胶囊与CSA口服溶液生物等效，且大多数患者更喜欢胶囊而非口服溶液。
