title: History of C2 monitoring in heart and liver transplant patients treated with cyclosporine microemulsion.
abstract: Therapeutic drug monitoring of CsA has evolved since the introduction of CsA microemulsion. The purpose of the present review is to summarize the history of CsA concentration 2 hours postdose (C2) monitoring in heart and liver transplantation. C2 has been shown to be the best single time point that correlates with the area-under-the-curve, with a correlation coefficient (r2) ranging between .83 and.93. C2 monitoring (300 to 600 ng/mL) has resulted in a significant clinical benefit in long-term heart and liver transplant patients compared to trough level (C0) monitoring. Moreover, a C2 range of 300 to 600 ng/mL resulted in a similar calcineurin inhibition compared to a C2 range of 700 to 1000 ng/mL or a C0 range of 100 to 200 ng/mL while being less injurious to renal function. In de novo liver transplant patients not receiving induction therapy, the achievement of a target C2 of 850 to 1400 ng/mL by postoperative day 3 has resulted in a low acute rejection rate. Furthermore, C2 monitoring has been associated with a lower rejection rate in hepatitis C virus (HCV)-negative patients and with an overall lesser severity of acute rejection compared to C0 monitoring. In de novo heart transplant patients who receive antithymocyte globulin induction, a lower C2 range may be sufficient to prevent rejection and renal dysfunction. Future studies should help to fine-tune the optimal C2 range in heart or liver transplant patients receiving induction therapy and different maintenance immunosuppressive combinations.
authors.affiliation: Department of Medicine, Royal Victoria Hospital, McGill Univesity Health Center, Montréal, Québec, Canada. marcelo.cantarovich@muhc.mcgill.ca
authors.forename: M
authors.initials: M
authors.lastname: Cantarovich
authors.forename: J
authors.initials: J
authors.lastname: Barkun
authors.forename: N
authors.initials: N
authors.lastname: Giannetti
authors.forename: R
authors.initials: R
authors.lastname: Cecere
authors.forename: J-G
authors.initials: JG
authors.lastname: Besner
authors.forename: J
authors.initials: J
authors.lastname: Tchervenkov
mesh_terms: D000284:Administration, Oral; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000266:history / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000266:history; D004655:Emulsions; D016027:Heart Transplantation / Q000276:immunology / Q000502:physiology*; D049673:History, 20th Century; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D016031:Liver Transplantation / Q000276:immunology / Q000502:physiology*
chemical_list: D065095:Calcineurin Inhibitors; D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine