title: Therapeutic monitoring of tacrolimus: aberrant results by an immunoassay with automated pretreatment.
abstract: OBJECTIVE
  The therapeutic monitoring of Tacrolimus (FK506) is necessary since low doses may cause graft rejection while overdosage is linked to nephrotoxicity, neurotoxicity, and many other adverse effects. Occasional notices of elevated values recorded in patients under maintenance regimen have prompted us to record all results exceeding the therapeutic range (>15 ng/mL) with no clinical signs or explanation and to compare the routine method (Siemens-Dade Dimension XPand) with other assays.
  
  
  METHODS
  Eighty-four whole blood samples from 8 patients have been assayed by Dimension and by one or more of three other commercial assays (CMIA and MEIA, Abbott; EMIT, Siemens-Dade). As a reference, an automated LC-MS/MS method has been performed.
  
  
  RESULTS
  In all cases the raised Tacrolimus values were observed only by ACMIA, while the correlation (r2) of the other assays with LC-MS/MS was excellent for CMIA (0.97) and good for MEIA (0.88) and EMIT (0.83). The aberrant results were often recorded over a span of several weeks or months and could not be ascribed to a common cause.
  
  
  CONCLUSIONS
  Abnormally high Tacrolimus results by the ACMIA method have been observed in 1% of the patients currently followed up in our Center. Since these results may lead to erroneous adjustments of the drug dosage, we suggest checking any elevated or clinically unexplained Tacrolimus result by the ACMIA assay with other method(s) requiring an external pretreatment.
authors.affiliation: Laboratorio Baldi Riberi, Ospedale S. Giovanni Battista Le Molinette, Torino, Italy. dmoscato@molinette.piemonte.it
authors.forename: Donatella
authors.initials: D
authors.lastname: Moscato
authors.forename: Antonello
authors.initials: A
authors.lastname: Nonnato
authors.forename: Rita
authors.initials: R
authors.lastname: Adamo
authors.forename: Maria
authors.initials: M
authors.lastname: Vancheri
authors.forename: Antonio
authors.initials: A
authors.lastname: Caropreso
mesh_terms: D000328:Adult; D000368:Aged; D001331:Automation; D002675:Child, Preschool; D002853:Chromatography, Liquid; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007166:Immunosuppressive Agents / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000097:blood*; D053719:Tandem Mass Spectrometry; D014180:Transplantation
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus