title: Ketoconazole-tacrolimus coadministration in kidney transplant recipients: two-year results of a prospective randomized study.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
authors.forename: Khalid Farouk
authors.initials: KF
authors.lastname: El-Dahshan
authors.forename: Mohamed Adel
authors.initials: MA
authors.lastname: Bakr
authors.forename: Ahmed Farouk
authors.initials: AF
authors.lastname: Donia
authors.forename: Ali El-Sayed
authors.initials: Ael-S
authors.lastname: Badr
authors.forename: Mohamed Abdel-Kader
authors.initials: MA
authors.lastname: Sobh
mesh_terms: D000293:Adolescent; D000328:Adult; D004338:Drug Combinations; D005260:Female; D006084:Graft Rejection / Q000209:etiology* / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007654:Ketoconazole / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D007166:Immunosuppressive Agents; D007654:Ketoconazole; D016559:Tacrolimus