C2 monitoring strategy for optimising cyclosporin immunosuppression from the neoral®1 formulation

被引:144
作者
Levy, GA [1 ]
机构
[1] Toronto Hosp, Toronto, ON M5G 2C4, Canada
关键词
D O I
10.2165/00063030-200115050-00001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Profiling of absorption of cyclosporin microemulsion (Neoral((R))) is a concept in therapeutic drug monitoring (TDM) designed to further optimise the clinical benefits of this formulation in transplant recipients. A single blood concentration measurement 2 hours after Neoral((R)) administration (Cz) has been shown in both Liver and kidney transplant recipients to be a significantly more accurate predictor of drug exposure than trough concentrations (C-0), and its use results in a reduction in the incidence and severity of cellular rejection. In a prospective trial in de novo renal transplant recipients, patients who achieved target concentrations for area under the concentration-rime curve over the first 4 hours postdose (AUC(0-4h)) of 4500 to 5500 ng (.) h/ml within 5 days of transplantation had a 7% incidence of histological acute rejection, compared with 37% rejection in those patients who did not achieve this target level. Of the single sampling points, C-2 correlates best with AUC(0-4h) (r(2) = 0.86); C-0 had the poorest correlation. In an international study in 21 centres examining the absorption profiling, C-2 samples were the most accurate predictors of AUC(0-4h) and freedom from rejection. In liver transplant recipients receiving Neoral((R))-based maintenance immunosuppression, adoption of Neoral((R)) C-2 monitoring identifies patients who are both over- and under-dosed, which is not distinguished by C-0 measurements. Further adjustment of C-2 to recommended targets, even at 5 and 10 years after transplantation, results in reduction in nephrotoxicity without exposing the patient to the risk of rejection. In summary, despite a level of simplicity comparable to C-0 measurement, Neoral((R)) absorption profiling, and specifically C-2 measurement, is a much more sensitive approach to assessing the pharmacokinetics and predicting the clinical effect of this formulation in the individual patient, with a consequent marked reduction in the incidence of acute cellular rejection and improved long term graft function.
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页码:279 / 290
页数:12
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