title: Limited sampling strategy for mycophenolic acid in Japanese heart transplant recipients: comparison of cyclosporin and tacrolimus treatment.
abstract: BACKGROUND
  The purpose of the study was to characterize the pharmacokinetics of mycophenolic acid (MPA) in Japanese heart transplant recipients and to find the time point that has the best correlation with the MPA area under the plasma concentration curve (AUC).
  
  
  RESULTS
  Twenty-two Japanese recipients treated with mycophenolate mofetil were evaluated in the study. Approximately 9 months after transplantation, the area under the MPA serum concentration-time curve from 0 to 12 h (AUC(0-12 h)) was evaluated. The MPA AUC(0-12 h) h values in the cyclosporine (CsA) and tacrolimus (FK) groups ranged from 13.11 to 50.98 mug . h/ml and from 39.19 to 93.18 mug . h/ml, respectively. Fourteen models were developed and analyzed for their ability to estimate the MPA AUC(0-12 h) based on a limited number of samples in the CsA group. Sixteen models were developed in the FK group. The best model for predicting the full MPA AUC(0-12 h) in the CsA group was a 3-time-point model that included C(0 h), C(1 h) and C(2 h) (r(2), 0.96; mean prediction error, 0.15+/-7.85%); a 2-time-point model that included C(0 h), and C(2 h) (r(2), 0.94; mean prediction error, 0.495+/-10.35%) was also reliable. In the FK group, a 3-time-point model that included C(1 h), C(2 h) and C(4h) (r(2), 0.73; mean prediction error, 2.73+/-17.09%) was the best model for predicting the full MPA AUC(0-12 h), but it was not reliable in clinical practice.
  
  
  CONCLUSIONS
  A 3-(C(0 h), C(1 h) and C(2 h)) and a 2-time-point model (C(0 h) and C(2 h)) are useful for predicting the full MPA AUC(0-12 h) in Japanese heart transplant recipients treated with CsA but not with FK.
authors.affiliation: Department of Pharmacy, National Cardiovascular Center, Fujishirodai, Suita, Japan. kwada@hsp.ncvc.go.jp
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Wada
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Takada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kotake
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ochi
authors.forename: Hideki
authors.initials: H
authors.lastname: Morishita
authors.forename: Kazuo
authors.initials: K
authors.lastname: Komamura
authors.forename: Noboru
authors.initials: N
authors.lastname: Oda
authors.forename: Akiko
authors.initials: A
authors.lastname: Mano
authors.forename: Tomoko S
authors.initials: TS
authors.lastname: Kato
authors.forename: Akihisa
authors.initials: A
authors.lastname: Hanatani
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakatani
mesh_terms: D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002648:Child; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D012044:Regression Analysis; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus