title: Co-administration of ketoconazole and tacrolimus therapy: a transplanted rat model.
abstract: OBJECTIVE
  The aim of this work is to study the safety and the effect of addition of ketoconazole to experimental kidney transplanted rat treated with tacrolimus and predicts the percentage of tacrolimus dose reduction.
  
  
  METHODS
  The material of this work included 60 male Sprague Dawely rats subjected to renal allotransplantation. They were equally divided into five groups: Group I: served as control group, Group II: received FK506 3.2 mg/kg/bw, Group III: received FK506 2 mg/kg/bw, Group IV: received FK506 1 mg/kg/bw, Group V: received FK506 1 mg/kg/bw plus Ketoconazole 20 mg/kg/day. FK506 trough level and laboratory investigations were determined at 0, 3, 7, 10, 14, and 27 days post-transplantation.
  
  
  RESULTS
  In all groups loss of body weight was observed at day 27 after treatment compared to that before transplantation. Serum creatinine significantly increased at day 27 compared to the basal level in groups treated with 1.0 and 3.2 mg FK506 (1.80 +/- 0.50 versus 0.39 +/- 0.06 P = 0.001) and (1.03 +/- 0.26 versus 0.50 +/- 0.07 P = 0.001) respectively, while for 2.0 mg or 1.0 mg plus keto groups, no significant differences in serum creatinine levels over time (0.56 +/- 0.22 versus 0.44 +/- 0.10 P = 0.106) and (0.55 +/- 0.30 versus 0.42 +/- 0.08 P=0.160) were observed.
  
  
  CONCLUSIONS
  Concomitant administration of Ketoconazole and FK506 in transplanted rat model is safe and results in increase of blood trough level concentration of FK506 with 50% reduction of its dose.
authors.affiliation: Urology and Nephrology Center, Zagazig University, Egypt. nashwabaraket@hotmail.com
authors.forename: Nashwa
authors.initials: N
authors.lastname: Barakat
authors.forename: Alaa
authors.initials: A
authors.lastname: Sabry
authors.forename: Amgad
authors.initials: A
authors.lastname: El-Agroudy
authors.forename: Samia
authors.initials: S
authors.lastname: Hawas
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abdel-Maboud
authors.forename: Mahasen A
authors.initials: MA
authors.lastname: El-Shair
authors.forename: M A
authors.initials: MA
authors.lastname: Ghoneim
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D019540:Area Under Curve; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007654:Ketoconazole / Q000008:administration & dosage*; D016030:Kidney Transplantation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000008:administration & dosage*; D000637:Transaminases / Q000097:blood; D014184:Transplantation, Homologous
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D003404:Creatinine; D000637:Transaminases; D007654:Ketoconazole; D016559:Tacrolimus