Tacrolimus exposure before and after the conversion
The main parameters of tacrolimus exposure determined in both study groups (expressors and non-expressors) determined after administration of the twice-daily and once-daily formulations are summarized in Table 2, and the blood concentration-time profiles of tacrolimus are shown in Figure 3. After the administration of tacrolimus, the median daily dose of the drug and the median dose/weight were significantly higher in the expressor group (P < 0.001). Despite this, the study groups did not differ significantly in terms of the median tacrolimus trough levels during the follow-up. The median dose-adjusted trough level (C0/dose) and dose/kg-adjusted trough level (C0/dose/kg) were significantly lower in the expressor group than in the non-expressor group (P < 0.001).
After the conversion to once-daily extended-release tacrolimus, median trough level of the drug (C0) decreased by nearly 25%; the change was similar regardless of the CYP3A5 genotype (- 24.0% in the expressor group vs. - 25.5% in the non-expressor group). Moreover, a decrease in the median dose-adjusted trough level and dose/kg-adjusted trough level was observed, by 42.9% and 40.0% in the expressor group, respectively, and by 26.1% and 23.7% in the non-expressor group, respectively. The decrease in the dose-adjusted trough level and dose/kg-adjusted trough level was significantly greater in the expressor group than in the non-expressor group (P < 0.001 and P < 0.001, respectively).