Donor's CYP3A‐status (CYP3A5 genotype and CYP3A4 expression)
can provide prognostic information regarding tacrolimus‐metabolizing capacity of the
liver graft and initial tacrolimus dosing for therapeutic blood concentrations in
liver transplants. The present work prospectively investigated whether CYP3A‐status
guided tacrolimus therapy has any potential clinical benefit for recipients in the
early postoperative period.MethodsThe
contribution of preliminary assaying of donor CYP3A‐status to the optimization of
initial tacrolimus therapy and to the reduction of adverse events (acute rejection,
infection, nephrotoxicity) was investigated in 112 liver transplant recipients (CYPtest
group) comparing to 101 control patients on tacrolimus concentration guided therapy.ResultsThe
time for achieving therapeutic tacrolimus concentration was significantly reduced,
confirming potential benefit of initial tacrolimus therapy adjusted to donor's CYP3A‐status
over classical clinical practice of tacrolimus concentration guided treatment (4 vs
8 days, P < 0.0001). Acute rejection episodes (3.6 vs
23.8%, P < 0.0001) and tacrolimus induced nephrotoxicity
(8 vs 27%, P = 0.0004) were
less frequent in CYPtest group than in control patients, whereas occurrence of infectious
disease was not influenced by tacrolimus dosing strategy (3.6 vs
5.9% in CYPtest and control groups, P > 0.05). Acute rejection
was often accompanied with tacrolimus blood concentrations lower than 10 ng mL−1
(20/24 of control and 2/4 of CYPtest patients), while nephrotoxicity was associated
with high tacrolimus concentrations (>20 ng mL−1) in the first
week after transplantation (13/27 of control and 2/9 of CYPtest patients).ConclusionCYP3A‐status
guided therapy significantly improved the risk of misdosing induced early adverse
effects (acute rejection, nephrotoxicity).
