Abstract
247 (Purpose) Tacrolimus is usually administered based on a mg/kg or the trough concentration (Cmin) in whole blood. But it is not easy to determine the optimal dose because of considerable interindividual variation of tacrolimus bioavailability between patients. Therapeutic drug monitoring of tacrolimus is mandatory. We investigated pharmacokinetics of tacrolimus in various conditioning renal transplant recipients. (Methods) Pharmacokinetic investigations were performed after kidney transplantation in various conditioning. 1) 30 patients were investigated in daily profile of tacrolimus blood levels. 2) 4 patients were evaluated the effects of meal timing on the bioavailability of tacrolimus. Tacrolimus was given to overnight fasted subjects and 0.5 hours after a breakfast in each patient. 3) 3 patients were taken grapefruit juice with tacrolimus and were measured tacrolimus level. (Results) There was a strong correlation between AUC and the trough concentration of tacrolimus (Cmin) in whole blood (r=0.745,P <0.001) and was only a weak correlation between dose per kilogram body-weight and AUC. Significant increases in the maximum concentration (Cmax) to 223% and in the AUC to 157% of 0.5 hours after the meal were seen in the overnight fasted subjects.TableThere was no significant effect in tacrolimus absorption in patients with grapefruit juice. Table(Conclusion) The strong correlation between AUC and the trough concentrations of tacrolimus (Cmin) indicates that trough levels are good indicators of systemic exposure. Since tacrolimus absorption was better under fasted conditions than under the presence of food, tacrolimus should be administered at least 1 hour before the meal. Co-administration of grapefruit juice was not useful in reducing tacrolimus dose in our study.
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