Tacrolimus is an immunosuppressive drug widely used after kidney transplantation. Because hematocrit is highly variable in kidney transplant patients and increases substantially after kidney transplantation, hematocrit is a key factor in the interpretation of tacrolimus whole blood concentrations. Fat-free mass, CYP3A5 genotype, sex, age and time after transplant influence the tacrolimus individual dose requirement. Hematocrit predicts variability in tacrolimus whole blood concentrations but is not expected to influence unbound (therapeutically active) concentrations. Bioavailability was highest immediately after transplantation, decreasing steeply thereafter to reach its nadir at day 5, following which it increased during the next 55 days towards an asymptotic value that was 28 % higher than that on day 5. Standardization of tacrolimus whole blood concentrations to a hematocrit value of 45 % improved the model fit significantly ( p 55 years that was 47 % higher than the male value at age <40 years. Population pharmacokinetic modeling was performed using NONMEM 7.2®. Methodsĭata on forty-four 12-h pharmacokinetic profiles from 29 patients and trough concentrations in 44 patients measured during the first 70 days after transplantation (1,546 tacrolimus whole blood concentrations) were analyzed. To identify patient characteristics that influence tacrolimus individual dose requirement in kidney transplant recipients.
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