Patients
The study participants received LT more than six months but no earlier
than three years before the enrollment. The inclusion criteria were: age
≥19 years, the use of twice-daily tacrolimus at screening, stable kidney
function (serum creatinine level, Cr <2.0 mg/dL) and liver
function (serum aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) levels within normal ranges), and maintenance of
the same immunosuppressive dosing regimen for ≥2 weeks before the
enrollment. The patients who received any drugs known to interfere with
tacrolimus pharmacokinetics and those enrolled in other
immunosuppressant study protocols were not eligible for the study. Other
exclusion criteria were: trough level of tacrolimus at screening
<2 ng/mL, an acute rejection episode within 90 days before the
enrollment, other organ transplant, renal dysfunction (serum Cr ≥2 mg/dL
or estimated glomerular filtration rate, eGFR <30mL/min),
clinically significant infection, a history of malignancy other than
hepatocellular carcinoma or skin cancer, recurrent hepatitis B virus, or
hepatitis C virus infection, liver dysfunction, pregnancy, or unstable
concurrent medical condition.
This was not a hypothesis driven study, but a pilot study to investigate
the effect of CYP3A5 polymorphism on liver function and trough
level of tacrolimus after conversion to the once-daily extended-release
tacrolimus formulation. The study patients were grouped based on the
expressions of CYP3A5 polymorphism (expressors vs.
non-expressors). The minimum required sample size was 30 patients per
group. This number was based on a general assumption that the variance
for a sample of at least 30 reflects the population variance quite
accurately, and hence, statistical testing that does not target a
specific hypothesis is valid. Therefore, our goal was to recruit a total
of 60 patients, 30 per group. The dropout rate was not considered in the
safety-oriented analysis. In addition, we performed a pharmacokinetic
analysis in 10 patients (5 per group) who agreed to participate in this
part of the study.