title: Evaluation and comparison of therapeutic monitoring of whole-blood levels of cyclosporin A and its metabolites in renal transplantation by HPLC and RIA methods.
abstract: BACKGROUND
  The aim of the work was to evaluate the possibility to estimate the level of cyclosporin A (CyA) metabolites as the difference of radioimmunoassay (RIA) non-specific and RIA specific methods.
  
  
  METHODS
  Blood samples of renal transplant patients were analyzed by three different methods: RIA specific method (CYCLO-Trac, DiaSorin, USA) (RIA(SP)), RIA non-specific method (Immunotech, Czech Republic) (RIA(NS)), and high performance liquid chromatography (HPLC) method.
  
  
  RESULTS
  Although values obtained by RIA(SP) correlated 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 obtained by RIA(NS) 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 metabolites)/(CyA) calculated as the ratio RIA(NS)/RIA(SP) values for 42 renal transplant patients was relatively stable for each particular patient. The sum of selected CyA metabolites (M1+M17+M21) measured by HPLC correlated well with that estimated from the difference of RIA(NS)-RIA(SP): HPLC(metab)=0.921.(RIA(NS)-RIA(SP))+21.3; (r(2)=0.746, n=448).
  
  
  CONCLUSIONS
  The combination of both the specific and non-specific methods for the determination of CyA presents an improved means for the TDM of CyA and CyA metabolites in renal transplant patients. Moreover, a combination of both methods can help to elucidate some unexpected events, such as the persistence of high cyclosporin blood levels.
authors.affiliation: Department of Nuclear Medicine, University Hospital and Medico-Social Faculty, University of Ostrava, 17. listopadu 1790, 708 52 Ostrava, Czech Republic. kristian.safarcik@fnsp.cz
authors.forename: K
authors.initials: K
authors.lastname: Safarcík
authors.forename: H
authors.initials: H
authors.lastname: Brozmanová
authors.forename: V
authors.initials: V
authors.lastname: Bartos
authors.forename: A
authors.initials: A
authors.lastname: Jegorov
authors.forename: M
authors.initials: M
authors.lastname: Grundmann
mesh_terms: D001774:Blood Chemical Analysis / Q000379:methods / Q000706:statistics & numerical data; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D016572:Cyclosporine / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000502:physiology*; D011863:Radioimmunoassay / Q000379:methods* / Q000706:statistics & numerical data; D012044:Regression Analysis
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine