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).