More Stable and Reliable Pharmacokinetics with Preprandial Administration of Cyclosporine Compared with Postprandial Administration in Patients with Refractory Nephrotic Syndrome

Study Objective. To compare the absorption profile of cyclosporine after preprandial administration with that after postprandial administration, and to determine which administration time resulted in a more stable absorption profile and the timing of the drug concentration that was the most reliable marker for monitoring drug absorption. Design. Prospective analysis. Setting. University teaching hospital in Japan. Patients. Sixteen patients with refractory nephrotic syndrome. Intervention. Thirteen patients received cyclosporine after breakfast (postprandial group) and eight received the drug 30 minutes before breakfast (preprandial group). Measurements and Main Results. Blood cyclosporine concentration was measured 5 times serially: before administration (C0) and at 1‐hour intervals until 4 hours after administration of cyclosporine (C1‐C4). Also, area under the concentration‐time curve from 0–4 hours (AUC0–4) was calculated. Of the 13 patients in the postprandial group, six (46%) showed fair absorption and exhibited a peak concentration at C1 or C2 (high‐absorption pattern); seven (54%) showed poor absorption and did not reach the peak concentration within the 4‐hour period (low‐absorption pattern). Five of the seven patients with the low‐absorption pattern were switched from postprandial to preprandial administration. All patients in the preprandial administration group showed a high‐absorption pattern and reached the peak cyclosporine concentration at C1. The C2 value showed the best correlation with AUC0–4 in both groups, and the C0 parameter did not correlate with AUC0–4 in either group. Conclusion. Preprandial administration provided a more stable absorption profile of cyclosporine compared with postprandial administration. From the correlation with AUC0–4, we concluded that C2, and not C0, is a reliable marker for monitoring cyclosporine exposure.