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


METHODS
Prospective analysis.


METHODS
University teaching hospital in Japan.


METHODS
Sixteen patients with refractory nephrotic syndrome.


METHODS
Thirteen patients received cyclosporine after breakfast (postprandial group) and eight received the drug 30 minutes before breakfast (preprandial group).


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.


CONCLUSIONS
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.
Kusaba
Tetsuro
T
Konno
Yusuke
Y
Hatta
Shigeo
S
Fujino
Tomoya
T
Yasuda
Takashi
T
Miura
Hiroshi
H
Sasaki
Hiroyo
H
Okabayashi
Jun
J
Murao
Mei
M
Sakurada
Tsutomu
T
Imai
Goro
G
Shirai
Sayuri
S
Kuboshima
Shingo
S
Shima
Yoshinori
Y
Ogimoto
Goichi
G
Sato
Takeo
T
Masuhara
Keisou
K
Kimura
Kenjiro
K
D000042:Absorption; D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005215:Fasting; D006785:Hospitals, University; D006801:Humans; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D019518:Postprandial Period; D011446:Prospective Studies; D012720:Severity of Illness Index; D013997:Time Factors
D016572:Cyclosporine