Improving the therapeutic monitoring of cyclosporin A

The narrow therapeutic window of cyclosporin A (CsA) and the variable pharm acokinetics of the traditional preparation, CsA-SIM (Sandimmune(TM)), have made it difficult to establish its optimal use. The introduction of a micro emulsion preparation, CsA-ME (Neoral(TM)), with less variable pharmacokinet ics, has made it possible to attempt to define its use more closely. One hu ndred and one renal allograft recipients were converted from CsA-SIM to CsA -ME. Absorption was monitored using a standard pharmacokinetic 'profile' me asuring 'whole blood' CsA levels at several time points following drug admi nistration. Areas under the resulting time-versus-CsA concentration curve ( AUC) were calculated. Surprisingly, many patients showed very little fluctu ation in 'whole blood' levels after administration of the conventional prep aration: 31% had a difference between trough (t(0)) and maximal levels of < 100 mu g/L. On microemulsion cyclosporin, there was much better correlatio n between AUC and several parameters incorporating elements of trough and p eak values. The best correlation was with t(0) + (t(1)/4), where t(1) repre sents the concentration at 1 h following administration? (r(2) = 0.779 for microemulsion cyclosporin). The use of this parameter is a practical possib ility in an out-patient setting. The very common, but under-recognised, pat tern of almost flat absorption profiles in patients on conventional CsA sug gests that the use of CsA in numerous clinical contexts should be reviewed, since CsA immunosuppression may previously have been inadequately monitore d.