Ann Transplant 2008; 13(1): 25-25
The purpose of this work is to summarize the current trends in tacrolimus (TAC) optimisation in transplant patients. Knowledge of the analytical method used to monitor TAC is mandatory (cross-reactivity, interferences, calibration bias, reproducibility, sensitivity, ...). Even more important is the ability to draw comparison among the different methods available (patients outcome according to TAC blood levels, multicenter clinical trials, ...). The choice of the analytical method should depend upon each laboratory characteristics (number of samples, staff experience, equipment, ...), and on the experience of clinicians with a particular method. Even though the vast majority of laboratories use immunoassays, implementation of LC-MS(MS) is increasing (2% in 1999, 19% in 2007). A large discussion exists about the most accurate approach to evaluate drug exposure or AUC (single time point -C0 or others-, limited sampling strategy or Bayesian estimates, ...). Most multi-centre trials (e.g. SYMPHONY study) stress the importance of concomitant therapies, time post-transplantation and transplant type, in defining appropriate TAC target concentrations. Recent data suggest a reduction in the recommended target TAC concentration down to 3-7 ng/mL when the drug is associated to daclizumab, MMF and steroids. Treatment management should also most likely take advantage of integrating the genetic polymorphism of proteins or enzymes involved in the tacrolimus drug disposition, in order to reach earlier optimal dosage regimen. TAC blood concentrations clearly correlate with the risk of side effects, whereas the relationship with efficacy seems much weaker. Research protocols are currently ongoing precisely to improve the predictability of the treatment efficacy (pharmacodynamic markers, drug concentration within target tissue, ...).
Keywords: cross-reactivity, biothecnology, proteomes