[Value of simultaneous determination of cyclosporin blood levels using specific and nonspecific methods in liver transplantation].
Cyclosporine's narrow therapeutic window and the large inter- and intra-individual variation of its pharmacokinetics require therapeutic monitoring. Cyclosporine is metabolized in the liver and excreted with its metabolite into the bile. An accumulation of metabolites occurs in liver dysfunction, leading to a high cyclosporine blood concentration when measured by a non-specific method (polyclonal antibodies). Specific methods (HPCL, monoclonal antibody) are therefore recommended by some authors. We evaluated the potential usefulness of simultaneous cyclosporine determination by a non-specific (fluorescent polarisation TDx, polyclonal antibodies) and a specific method (I125-RIA, monoclonal antibody). 10 patients were followed from 51 days to 32 months after hepatic transplantation. 2 patients who showed no graft rejection presented a polyclonal antibodies/monoclonal antibody ratio below or equal to 4 throughout their evolution. Other patients presented a rise of this ratio during periods of liver dysfunction, particularly in acute graft rejection. When bilirubin concentrations are plotted versus this ratio, an hysteresis is present during periods of acute rejection, but not during an episode of histological hepatitis. The same holds true for alkaline phosphatase and gamma-GT. These data suggest that this ratio could be a sensitive test for early detection of rejection. Simultaneous cyclosporine blood determination with specific and nonspecific methods may be useful in the follow-up of liver-transplanted patients.
Piguet
V
V
Division de pharmacologie clinique, CHUV, Lausanne.
Mosimann
F
F
Genton
A
A
Appenzeller
M
M
Munafo
A
A
Bachmann
C
C
Biollaz
J
J
D000328:Adult; D016572:Cyclosporine / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007158:Immunologic Techniques; D008099:Liver / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D016719:Radioimmunodetection; D012680:Sensitivity and Specificity
D016572:Cyclosporine
Intérêt de la détermination simultanée des taux sanguins de ciclosporine par méthodes spécifique et non spécifique chez le transplanté hépatique.