Tacrolimus - Pharmacokinetic Considerations for Clinicians

Background: The calcineurin inhibitor tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, clinical management of Tac therapy can be challenging because of its narrow therapeutic window and because many factors interfere with its metabolism. Therefore, therapeutic drug monitoring is used to adjust the dosage. Method: Recently, we were able to classify patients receiving tacrolimus into two major metabolism groups by simple calculation of the C/D ratio (expressed as the blood concentration normalized by the dose). Results: We showed that the C/D ratio is significantly associated with the (renal) outcome of recipients after kidney and liver transplantation. Conclusion: These findings are interesting and relevant to transplant physicians and physicians interested in immunosuppressive therapy. We therefore review current state of the art aspects of tacrolimus pharmacokinetics including genetics or different tacrolimus formulations (twice-daily immediate-release tacrolimus capsules, once-daily extended- release tacrolimus capsules; novel once-daily tacrolimus tablets) and their possible clinical impact including practical considerations for clinicians. Keywords: Tacrolimus, tacrolimus pharmacokinetics, tacrolimus formulation, tacrolimus metabolism, kidney transplantation, renal transplantation.