Optimization of the use of Calcineurin inhibitors in liver transplantation

• Published in: Baillière's best practice & research. Clinical gastroenterology Vol. 26; no. 1; pp. 85 - 95
• Main Authors: de Mare-Bredemeijer, E.L.D., MD, Metselaar, H.J., MD, PhD
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.02.2012; Elsevier Limited
• Subjects: Calcineurin inhibitor; Calcineurin Inhibitors; Cyclosporine - adverse effects; Cyclosporine - therapeutic use; Diabetes Mellitus - chemically induced; Drug Administration Schedule; Drug Substitution - methods; Gastroenterology and Hepatology; Graft Rejection - immunology; Graft Rejection - prevention & control; Hepatitis C - immunology; Humans; Hypertension - chemically induced; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - metabolism; Immunosuppressive Agents - therapeutic use; Kidney Failure, Chronic - chemically induced; Liver Transplantation - immunology; Metabolism; Minimization; mTOR inhibitor; Rend dysfunction; Tacrolimus - adverse effects; Tacrolimus - metabolism; Tacrolimus - therapeutic use; TOR Serine-Threonine Kinases - antagonists & inhibitors; mTOR inhibitor; Minimization; Calcineurin inhibitor; Rend dysfunction; Metabolism
• ISSN: 1521-6918; 1532-1916
• DOI: 10.1016/j.bpg.2012.01.017

Calcineurin inhibitors (CNIs), such as cyclosporin A and tacrolimus, are the cornerstone of maintenance immunosuppressive regimens in liver transplantation. CNIs prevent rejection by inhibition of calcineurin, via which lymphocyte proliferation and interleukin (IL)-2 production is prevented. Tacrolimus is now the first-choice immunosuppressant after liver transplantation, since it is associated with fewer episodes of rejection than cyclosporin A. In this review we will discuss interindividual differences, which influence tacrolimus metabolism. Because of these factors and the narrow therapeutic index of tacrolimus, monitoring of drug trough levels is necessary. Furthermore, we will discuss studies concerning conversion from the tacrolimus twice daily to tacrolimus once daily formulation in stable LT patients. Due to adverse effects of CNIs, such as chronic renal failure, hypertension, de novo malignancy and new-onset diabetes mellitus, CNI minimization strategies have been developed, which will be discussed too.