title: More stable and reliable pharmacokinetics with preprandial administration of cyclosporine compared with postprandial administration in patients with refractory nephrotic syndrome.
abstract: 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.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kusaba
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Konno
authors.forename: Shigeo
authors.initials: S
authors.lastname: Hatta
authors.forename: Tomoya
authors.initials: T
authors.lastname: Fujino
authors.forename: Takashi
authors.initials: T
authors.lastname: Yasuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miura
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Sasaki
authors.forename: Jun
authors.initials: J
authors.lastname: Okabayashi
authors.forename: Mei
authors.initials: M
authors.lastname: Murao
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sakurada
authors.forename: Goro
authors.initials: G
authors.lastname: Imai
authors.forename: Sayuri
authors.initials: S
authors.lastname: Shirai
authors.forename: Shingo
authors.initials: S
authors.lastname: Kuboshima
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Shima
authors.forename: Goichi
authors.initials: G
authors.lastname: Ogimoto
authors.forename: Takeo
authors.initials: T
authors.lastname: Sato
authors.forename: Keisou
authors.initials: K
authors.lastname: Masuhara
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kimura
mesh_terms: 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
chemical_list: D016572:Cyclosporine