Impact of ketoconazole on fk506 in microsurgical kidney transplantation in rates

This work aimed to study the effect of additional dose of Ketoconazole tothe experimental kidney transplanted rat model, which is treated with tacrolimus (FK506), and precludes the optimal tacrolimus dose reduction. Rats were first undergoes kidney transplantation according to Zheng et al., 1995 where the right renal transplanaortic cuff to the aorta of the recipient, the donor venous cuff to the inferior vena •cava of the recipient by running suture technique using 1 % ethilon, and theurinary tract reconstruction was accomplished by suturing the donor bladder patch to the recipient bladder using 6/0 PDS. Tacrolimus (FK506) a macrolide lactone with potent immunosuppressive properties was approved in 1994 for prevention of graft rejectiokidney transplantation. Hepatic metabolism of tacrolimus occurs via themicrosomal cytochorome P450 3A4-isoenzyme. Thus, concurrent use ofsubstances known to inhibit or induce cytochorome p450-3A4 activity mayinfluence the metabolism of tacrolimus, resulting in an increase or decrease inwhole blood concentrationKetoconazole antifungal drug was found to be extensively cytocrome p4503A4 inhibitor, so coadminstration of ketoconazole and FK06 leads to inhibition of FK506 metabolism and consequently increase in its blood levelRats were divided into five groups according to the dose of FK506, whichwere 0, 3.2mg/kg/day, 2.0mg/kg/day, 1.0mg/kg/day and 1.0mg/kg/day plus20mg Ketoconazole/kg/day.Serum biochemical: