Evaluation and comparison of therapeutic monitoring of whole-blood levels of cyclosporin A and its metabolites in renal transplantation by HPLC and RIA methods

Background: The aim of the work was to evaluate the possibility to estimate the level of cyclosporin A (CyA) metabolites as the difference of radioimm unoassay (RIA) non-specific and RIA specific methods. Methods: Blood sample s of renal transplant patients were analyzed by three different methods: RI A specific method (CYCLO-Trac, DiaSorin, USA) (RIA(SP)), RIA non-specific m ethod (Immunotech, Czech Republic) (RIA(NS)), and high performance liquid c hromatography (HPLC) method. Results: Although values obtained by RIA(SP) c orrelated well those obtained by HPLC (RIA(SP) = 0.995 HPLC + 9:68; r(2) = 0.962, n = 448), the results of HPLC methods were lower by 8%. The values o btained by RIA, were 2.57 times higher than the values obtained by RIA(SP) (RIA(SP) = 0.356RIA(NS); r(2) = 0.713, n = 448). The ratio (CyA + CyA metab olites)/(CyA) calculated as the ratio RIA(NS)/RIA(SP) values for 42 renal t ransplant patients was relatively stable for each particular patient. The s um of selected CyA metabolites (M1 + M17 + M21) measured by HPLC correlated well with that estimated from the difference of RIA(NS) - RIA(SP): HPLCmet ab = 0.921 . (RIA(NS) - RlA(SP)) + 21.3; (r2 = 0.746, n = 448). Conclusion: The combination of both the specific and non-specific methods for the dete rmination of CyA presents an improved means for the TDM of CyA and CyA meta bolites in renal transplant patients. Moreover, a combination of both metho ds can help to elucidate some unexpected events, such as the persistence of high cyclosporin blood levels. (C) 2001 Elsevier Science B.V. All rights r eserved.