Early adequate mycophenolic acid exposure is associated with less rejection in kidney transplantation

被引:122
作者
Kiberd, BA [1 ]
Lawen, J
Fraser, AD
Keough-Ryan, T
Belitsky, P
机构
[1] Capital Hlth, Dept Med, Halifax, NS, Canada
[2] Capital Hlth, Dept Urol, Halifax, NS, Canada
[3] Capital Hlth, Dept Pathol, Halifax, NS, Canada
[4] Dalhousie Univ, Halifax, NS, Canada
关键词
absorption profile monitoring; cyclosporine; mycophenolate mofetil; pharmacodynamics; pharmacokinetics; rejection; therapeutic drug monitoring;
D O I
10.1111/j.1600-6143.2004.00455.x
中图分类号
R61 [外科手术学];
学科分类号
摘要
This study examines the importance of early mycophenolic acid (MPA) exposure in the cyclosporine- and mycophenolate mofetil (MMF)-treated kidney transplant population. We prospectively evaluated 94 first solitary kidney transplant patients treated with cyclosporine (Neoral), MMF, and prednisone. Basiliximab was also given to 72 recipients. MPA exposure was measured by HPLC using a limited sampling estimate of 12 h area under the curve (AUC [0-12]) within the first week. Efficacy was determined by the occurrence of acute rejection and toxicity by the need to reduce MMF doses within the first 3 months post-transplantation. Acute rejection was observed in 14 (15%) and MMF toxicity in 27 (29%). Receiver operator curve analysis shows that MPA AUC [0-12] on day 3 was predictive of efficacy (c = 0.72, p = 0.007) but not toxicity (c = 0.57, p = 0.285). A separate analysis of only patients on basiliximab shows that the MPA AUC [0-12] on day 3 was also predictive of efficacy (c = 0.80, p = 0.01). Therefore early adequate exposure to MPA by day 3 is associated with low acute rejection but cannot predict toxicity. Adequate MPA exposure is also important with basiliximab induction therapy.
引用
收藏
页码:1079 / 1083
页数:5
相关论文
共 20 条
[1]   Anti-CD25 monoclonal antibody therapy affects the death signals of graft-infiltrating cells after clinical heart transplantation [J].
Baan, CC ;
Balk, AHMM ;
van Riemsdijk, IC ;
Vantrimpont, PJMJ ;
Maat, APWM ;
Niesters, HGM ;
Zondervan, PE ;
van Gelder, T ;
Weimar, W .
TRANSPLANTATION, 2003, 75 (10) :1704-1710
[2]   Basiliximab widens the therapeutic window for AUC-monitored neoral therapy early after kidney transplantation [J].
Balbontin, F ;
Kiberd, B ;
Singh, D ;
Squires, J ;
Fraser, A ;
Belitsky, P ;
Lawen, J .
TRANSPLANTATION PROCEEDINGS, 2003, 35 (07) :2409-2411
[3]  
BELITSKY P, 2003, TRANSPLANT P, V32, P10
[4]   Adequate early cyclosporin exposure is critical to prevent renal allograft rejection: Patients monitored by absorption profiling [J].
Clase, CM ;
Mahalati, K ;
Kiberd, BA ;
Lawen, JG ;
West, KA ;
Fraser, AD ;
Belitsky, P .
AMERICAN JOURNAL OF TRANSPLANTATION, 2002, 2 (08) :789-795
[5]   Mycophenolate mofetil for solid organ transplantation: Does the evidence support the need for clinical pharmacokinetic monitoring? [J].
Cox, VC ;
Ensom, MHH .
THERAPEUTIC DRUG MONITORING, 2003, 25 (02) :137-157
[6]   WOFIE synergizes with calcineurin. inhibitor treatment and early steroid withdrawal in kidney transplantation [J].
Dresske, B ;
Zavazava, N ;
Jenisch, S ;
Exner, B ;
Lenz, P ;
El Mokhtari, NE ;
Kremer, B ;
Faendrich, F .
TRANSPLANTATION, 2003, 75 (08) :1286-1291
[7]   The pharmacokinetic-pharmacodynamic relationship for mycophenolate mofetil in renal transplantation [J].
Hale, MD ;
Nicholls, AJ ;
Bullingham, RES ;
Hené, R ;
Hoitsma, A ;
Squifflet, JP ;
Weimar, W ;
Vanrenterghem, Y ;
Van de Woude, FJ ;
Verpooten, GA .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1998, 64 (06) :672-683
[8]   Mycophenolate mofetil in renal allograft recipients - A pooled efficacy analysis of three randomized, double-blind, clinical studies in prevention of rejection [J].
Halloran, P ;
Mathew, T ;
Tomlanovich, S ;
Groth, C ;
Hooftman, L ;
Barker, C .
TRANSPLANTATION, 1997, 63 (01) :39-47
[9]   Improved graft survival after renal transplantation in the United States, 1988 to 1996. [J].
Hariharan, S ;
Johnson, CP ;
Bresnahan, BA ;
Taranto, SE ;
McIntosh, MJ ;
Stablein, D .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 342 (09) :605-612
[10]  
Hong JC, 2000, SEMIN NEPHROL, V20, P108