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More stable and reliable pharmacokinetics with preprandial administration of cyclosporine compared with postprandial administration in patients with refractory nephrotic syndrome.

Abstract：

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 (C 0 ) and at 1-hour intervals until 4 hours after administration of cyclosporine (C 1 -C 4 ). Also, area under the concentration-time curve from 0-4 hours (AUC 0-4 ) was calculated. Of the 13 patients in the postprandial group, six (46%) showed fair absorption and exhibited a peak concentration at C 1 or C 2 (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 C 1 . The C 2 value showed the best correlation with AUC 0-4 in both groups, and the C 0 parameter did not correlate with AUC 0-4 in either group. CONCLUSION:Preprandial administration provided a more stable absorption profile of cyclosporine compared with postprandial administration. From the correlation with AUC 0-4 , we concluded that C 2 , and not C 0 , is a reliable marker for monitoring cyclosporine exposure.

journal_name

Pharmacotherapy

journal_title

Pharmacotherapy

authors

Kusaba T,Konno Y,Hatta S,Fujino T,Yasuda T,Miura H,Sasaki H,Okabayashi J,Murao M,Sakurada T,Imai G,Shirai S,Kuboshima S,Shima Y,Ogimoto G,Sato T,Masuhara K,Kimura K

doi

10.1592/phco.25.1.52.55617

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

52-8

issue

eissn

0277-0008

issn

1875-9114

journal_volume

pub_type

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More stable and reliable pharmacokinetics with preprandial administration of cyclosporine compared with postprandial administration in patients with refractory nephrotic syndrome.