*4.1.1.1. Trough concentration (C0) monitoring*

Over the past two decades, there have been changes to recommended CsA dosing, changes in concomitant medications, and one major change to the oral drug formulation. Lately, there has also been the introduction of generic formulations of CsA [75]. In 1988, in a prospective study showed that although C0 (trough concentration) levels of CsA correlated poorly with dose, Cmax was significantly correlated with dose, Area Under the Curve (AUC) and elimi‐ nation half-life (t1/2). Those who suffered acute rejection had a significantly lower Cmax by 15– 31% [76]. The problem with this method for adjusting the dosage of CsA is that it relies on only one aspect of CsA pharmacokinetics, the predose or trough concentration. With the original formulation of CsA, Sandimmune®, this was the best practice, but during the conversion of patients from that formulation to the improved formulation, Neoral® the 2 h post-dose concentration has been advocated as a single concentration monitoring alternative to C0 [77]. The microemulsion formulation of CsA, Neoral®, makes CsA pharmacokinetics more predictable and reduces the effects of bile and food on absorption [78]. Nevertheless the predose concentration is still widely used in clinical practice. Currently, most transplant centers measure a single steady-state CsA concentration as either a C0 predose trough or 2 hours postdose, while some conduct multiple measurements to determine CsA AUC estimates [79]. The target predose concentrations varied not only with transplanted organ and time after transplant but also with the analytical method used. The therapeutic range of CsA used by clinicians varies greatly according to the type of assay used to measure CsA and whether blood or serum concentrations are determined by the clinical laboratory.

Thus, it has reported by high pressure liquid chromatography, monoclonal fluorescence polarization immunoassay (monoclonal TDx assay, Abbott Diagnostics®), or monoclonal radioimmunoassay (various manufacturers), the level of therapeutic concentrations in blood are 10-400 ng/mL. By high pressure liquid chromatography, monoclonal fluorescence polari‐ zation immunoassay (monoclonal TDx assay, Abbott Diagnostics®), or monoclonal radioim‐ munoassay (various manufacturers), the level of therapeutic concentrations in serum are 50-150 ng/mL. By polyclonal fluorescence polarization immunoassay (monoclonal TDx assay, Abbott Diagnostics®), or polyclonal radioimmunoassay (various manufacturers) the level of therapeutic concentrations in blood are 200-800 ng/mL, and by polyclonal fluorescence polarization immunoassay (monoclonal TDx assay, Abbott Diagnostics®), or polyclonal radioimmunoassay (various manufacturers), the level of therapeutic concentrations in plasma are 100-400 ng/mL [79].
