Co-administration of ketoconazole and tacrolimus therapy: a transplanted rat model.
OBJECTIVE
The aim of this work is to study the effect of addition of ketoconazole to experimental kidney transplanted rat treated with tacrolimus and precludes 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 mg and 3.2 mg FK506 (1.80+/-0.50 vs. 0.39+/-0.06 P=0.001) and (1.03+/-0.26 vs. 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 vs. 0.44+/-0.10 P=0.106) and (0.55+/-0.30 vs. 0.42+/-0.08 P=0.160) were observed.


CONCLUSIONS
Concomitant administration of ketoconazole and FK506 is safe and results in increase blood trough level concentration of FK506 with 50% dose reduction in transplanted rat model.
Sabry
Alaa
A
Mansoura Urology and Nephrology Center, Mansoura University, Mansoura, Egypt. asabry20@yahoo.com
El-Agroudy
Amgad
A
Sheashaa
Hussein
H
Hawas
Samia
S
El-Shahat
Fagr B
FB
Barakat
Nashwa
N
D000818:Animals; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007654:Ketoconazole / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000008:administration & dosage*
D007166:Immunosuppressive Agents; D007654:Ketoconazole; D016559:Tacrolimus