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Therapeutic Drug Monitoring

Methods of monitoring therapy with CNIs have become an established part of clinical practice. The reasons for this include: the potential for serious toxicity with CNIs, the importance of maintaining immunosuppressive efficacy to protect life-sustaining organ transplants, the wide range of variation between individuals in bioavailability and metabolism together with the large number of drug interactions between CNIs and other agents (Banner and Lyster 2003). Guidelines have been developed for the monitoring of ci-closporin and tacrolimus (Jusko et al. 1995; Oellerich et al. 1995).

The concentrations measured are those in whole blood and are only indirectly related to those at the site of action (Holt et al. 1994; Oellerich et al. 1998). Consequently, the TDM results must be interpreted in the light of other information including efficacy (lack of acute rejection) and toxicity (particularly renal). A 'therapeutic range' derived for a population of patients is usually wide and individuals with drug levels within the range may still experience rejection, nephrotoxicity or opportunistic infection. The appropriate therapeutic range will be determined by a series of factors including the time after transplantation and the other immunosuppressive agents being used (Banner and Lyster 2003). The choice of a specific 'target range' for an individual patient remains a matter of clinical judgement which must be based on the patient's individual response.

'Trough levels' are usually measured just before the administration of the next dose. In the case of tacrolimus, such levels appear to be a good measure of systemic exposure to the drug (Jusko et al. 1995). However, the correlation of trough level to exposure is less good in the case of the Neoral formulation of ciclosporin, and alternatives, such as the blood concentration 2 h after an oral dose, appear to be better measures (Levy 2001).

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