A Single Centered, Prospective, Open-labeled, Pharmacokinetic Pilot Study of Tacrolimus Administration via Rectiole

Tacrolimus is generally administered orally. Absorption of tacrolimus is often
disturbed due to gut immobility, which is often observed shortly after
transplantation or in case of septic shock. This can result in organ rejection
and toxicity of tacrolimus. Therefore, tacrolimus is then administered
intravenously. The intravenous administration has its disadvantages due to
toxicity of the dissolvent. Thus, another route of administration is necessary.
Therefore, we planned to study whether tacrolimus administration via rectiole
can be an alternative route.

To determine the tacrolimus bioavailability after tacrolimus administration via
a rectiole.

We will perform a multiple doses, prospective, open-labeled and single-centered
pilot study in patients treated with tacrolimus via a rectiole. Whole blood
tacrolimus concentrations will be analyzed on the first day, when tacrolimus
administration will be intravenously and from the second to the third day, when
tacrolimus is administered via a rectiole. Pharmacokinetic variables will be
analyzed, such as F, Cmax, Cmin, Tmax, T1/2, Vd, and AUC.

Subjects in this study donate more blood than in daily practice (7 ml instead
of 1 ml per day). Thus circa 18 ml extra blood for 3 days will be drawn. Extra
blood sampling will cause no supplementary pain since intensive care patients
are already equipped with an arterial line. We expect only minimal extra risk
in the research subjects related to the administration of tacrolimus as
rectiole and the sampling of the blood.