Influence of everolimus on cyclosporine Neoral pharmacokinetics in Chinese de novo cardiac transplant recipients.
OBJECTIVE
This study sought to determine the influence of everolimus on cyclosporine Neoral (CsA) pharmacokinetics over the first 6 months after heart transplantation in Chinese recipients.


METHODS
Six de novo cardiac recipients receiving a CsA-everolimus-based immunosuppressive regimen after rabbit antithymoglobulin sequential immuno-induction were compared with six age-matched recipients receiving a CsA-azathioprine-based regimen. We compared CsA 12-hour area-under-curve (AUC) of the first dose (PK-1) and steady state dose (PK-S) at 1 month after transplantation. The CsA trough concentrations (Cmin) were compared over the first 6 months after transplantation.


RESULTS
There was no significant difference between the two groups in age, gender, and body weight. With respect to dose-normalized CsA AUC(0-infinity) of PK-1 and dose-normalized CsA AUC(0-12) of PK-S, the difference between the everolimus- and the azathioprine-based regimens was not significant. The dose-normalized CsA trough concentrations (Cmin/dose) were significantly lower in the everolimus-based group than in the azathioprine-based group during the first 5 months after heart transplantation, but the difference was not significant at posttransplantation month 6.


CONCLUSIONS
When CsA pharmacokinetic profiles were considered, the CsA dose requirement was not lower in Chinese patients receiving everolimus than that in patients receiving azathioprine. The results differed from reports from Western countries.
Wang
C-H
CH
Department of Surgery, National Taiwan University Hospital and College of Medicine, No. 7 Chung-shan South Road, Taipei City, Taiwan.
Chou
N-K
NK
Wu
F-L L
FL
Ko
W-J
WJ
Tsao
C-I
CI
Chi
N-H
NH
Hsu
R-B
RB
Wang
S-S
SS
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D002681:China; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D001379:Azathioprine; D020123:Sirolimus