Background: The aim of this study was the retrospective evaluation of the relationship between the dosage of tacrolimus and its blood concentrations in renal transplant patients and assessment of the relationship between blood drug levels and the pharmacological effect.
Material/Methods: The studied group consisted of 64 patients (42 men and 22 women) on combined immunosuppressive treatment using tacrolimus (T), prednisolone (P), mycophenolate (M), azthioprine (A) and sirolimus (S) in various combinations including tacrolimus. The tacrolimus doses ranged from 0.05 to 0.3 mg/kg/day. During the 32-42 weeks follow-up whole blood tacrolimus levels were measured with microparticle enzyme immunoassay on IMx analyzer.
Results: No significant correlation between tacrolimus doses and its blood concentrations was found. Drug levels were within the subtherapeutic range in 89.1% of patients during the entire follow-up. In remaining patients 75-92.3% of results were also subtherapeutic, less than 25% of results were in the therapeutic range, no toxic levels were obtained. The graft rejection was observed in 10.9% patients, men only, 6 on T-P-M treatment (15.8% of T-P-M group) and one on T-P-A treatment. Acute tubular necrosis was observed in
21.9% of patients, 9 men (8 on T-P-M and 1 on T-P-A treatment) and 5 women (2 on T-P-M, 2 on T-P-A and 1 on T-P treatment). All graft rejections and ATN episodes occurred with sub-therapeutic tacrolimus concentrations. Conclusions: No significant dose-concentrations relationship indicates the need for individualized, empiric dosage and therapeutic monitoring of tacrolimus. In majority of studied patients the combined immunosupressive treatment including tacrolimus in subtherapeutic blood levels was effective. Thus, separate therapeutic ranges should be established for combined treatment and for both sexes. On the other hand subtherapeutic drug levels were found in all patients with graft rejection. However, these rejection episodes can not be explained solely by sub-therapeutic tacrolimus concentrations.

Keywords: Tacrolimus, mycophenolate, Cytocheratin 7