Therapeutic drug monitoring of sirolimus

Abstract

The pharmacology of the sirolimus and their use in renal transplant recipients are discussed here. In majority of the transplant centers, sirolimus whole-blood concentrations are measured by enzyme-linked immunoassays and high-performance liquid chromatography (HPLC) with ultraviolet or mass spectrometry detection. HPLC measures the parent drug and is very accurate but time-consuming. The recommended time for collection is 1 h prior to the next oral dose. Because of metabolic interactions, sirolimus should be given 4 h after cyclosporine, whereas sirolimus and Tacrolimus can be given simultaneously. The target sirolimus levels should be 5–15 ng/mL depending on immunologic risk, time of conversion and other immunosuppressive drugs. Sirolimus trough concentrations >15 ng/mL have been correlated with side effects such as hypertriglyceridemia, thrombocytopenia, and leukopenia. The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines for the care of kidney transplant recipients suggest monitoring sirolimus levels (2C). KDIGO recommend that if sirolimus is used, they should not be started until graft function is established and surgical wounds are healed (1B). KDIGO recommend that the combined use of sirolimus and calcineurin inhibitor (CNI) should be avoided, because they potentiate nephrotoxicity, particularly if used in the early period following transplantation. Conversion from CNI to sirolimus is generally not recommended when proteinuria >800 mg/day, acute rejection during the 3 months before conversion, estimated GFR < 40 mL/min, acute Banff 2A at any time post-transplant and dyslipidemia despite lipid lowering agents.