Bioavailability and Patient Acceptance of Cyclosporine Soft Gelatin Capsules in Renal Allograft Recipients

Abstract

OBJECTIVE: 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. METHODS: 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 (Tmax), 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. RESULTS: 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>0.1). The bioavailability was not significantly different between capsules and solutions when it was measured by PFIA assay (p>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. CONCLUSIONS: CSA oral soft gelatin capsule is bioequivalent to CSA oral solution and most patients preferred the capsule to the oral solution.