Ketoconazole-tacrolimus coadministration in kidney transplant recipients: Two-year results of a prospective randomized study

被引:25
作者
El-Dahshan, Khalid Farouk [1 ]
Bakr, Mohamed Adel [1 ]
Donia, Ahmed Farouk [1 ]
Badr, Ali El-Sayed [1 ]
Sobh, Mohamed Abdel-Kader [1 ]
机构
[1] Mansoura Univ, Urol & Nephrol Ctr, Mansoura, Egypt
关键词
ketoconazole-tacrolimus kidney transplant;
D O I
10.1159/000094133
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background/Aims: In developing countries, kidney transplantation is greatly hindered by financial problems, especially due to costly newer immunosuppressive medications. Ketoconazole increases blood levels of tacrolimus and cyclosporine through inhibition of cytochrome P450 microsomal enzymes. We previously reported on the 6-month safety and the outstanding impact on treatment costs of the ketoconazole-tacrolimus combination in kidney transplant recipients. Data of this combination are still lacking in the literature. We hereby report on the 2-year results of our trial. Methods: This prospective, randomized study included 70 live-donor kidney transplant recipients receiving tacrolimus (age 16-45 years, 54 males and 16 females). Patients were randomized into two equal groups: group 1, where ketoconazole 100 mg/day was added, and group 2 (control group). Results: After 2 years, group 1 (ketoconazole) patients still showed a highly significant reduction of the tacrolimus dose (by 53.8%) and cost (by 52.9%) compared with the control group (p < 0.001) and a significant improvement in graft function in comparison to their own initial graft function (p = 0.002). Throughout the 2 years, no side effects of ketoconazole were noted. Conclusion: We conclude that the long-term ketoconazole-tacrolimus combination therapy in kidney transplant recipients during the 2 years is safe, has an outstanding impact on treatment costs and improves graft outcome. Copyright (c) 2006 S. Karger AG, Basel.
引用
收藏
页码:293 / 298
页数:6
相关论文
共 18 条
[1]   A prospective, randomized study of coadministration of ketoconazole and cyclosporine A in kidney transplant recipients: Ten-year follow-up [J].
El-Agroudy, AE ;
Sobh, MA ;
Hamdy, AF ;
Ghoneim, MA .
TRANSPLANTATION, 2004, 77 (09) :1371-1376
[2]   Co-administration of ketoconazole to tacrolimus-treated kidney transplant recipients: a prospective randomized study [J].
El-Dahshan, KF ;
Adel Bakr, M ;
Donia, AF ;
Badr, AES ;
Sobh, MAK .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2004, 19 (06) :1613-1617
[3]   Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients [J].
Emre, S ;
Genyk, Y ;
Schluger, LK ;
Fishbein, TM ;
Guy, SR ;
Sheiner, PA ;
Schwartz, ME ;
Miller, CM .
TRANSPLANT INTERNATIONAL, 2000, 13 (01) :73-78
[4]  
FERGUSON RM, 1982, LANCET, V2, P882
[5]   EFFECTS OF KETOCONAZOLE ON METHYLPREDNISOLONE PHARMACOKINETICS AND CORTISOL SECRETION [J].
GLYNN, AM ;
SLAUGHTER, RL ;
BRASS, C ;
DAMBROSIO, R ;
JUSKO, WJ .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1986, 39 (06) :654-659
[6]   THE EFFECTS OF KETOCONAZOLE ON THE INTESTINAL METABOLISM AND BIOAVAILABILITY OF CYCLOSPORINE [J].
GOMEZ, DY ;
WACHER, VJ ;
TOMLANOVICH, SJ ;
HEBERT, MF ;
BENET, LZ .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1995, 58 (01) :15-19
[7]  
JONES HE, 1987, KETOCONAZOLE TODAY R, P8
[8]  
LEWIS JH, 1984, GASTROENTEROLOGY, V86, P503
[9]  
Möller A, 1999, DRUG METAB DISPOS, V27, P633
[10]   A case of tacrolimus nephrotoxicity appearing in a second renal transplantation patient [J].
Oka, K ;
Moriyama, T ;
Imai, E ;
Kyo, M ;
Toki, K ;
Tanaka, T ;
Hori, M ;
Kokado, Y ;
Okuyama, A ;
Takahara, S .
CLINICAL TRANSPLANTATION, 2001, 15 :30-34