Medizinische Universität Graz - Research portal
Selected Publication:
Khoschsorur, G; Auer, T; Lanzer, G; Petritsch, P; Holzer, H; Tscheliessnigg, KH.
The determination of metabolite M17 and its meaning for immunosuppressive cyclosporin therapy.
Angiology. 1998; 49(4):307-314
Doi: 10.1177/000331979804900409
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
- Khoschsorur Gholamali
- Co-authors Med Uni Graz
- Auer-Schönbach Thomas
- Holzer Herwig
- Lanzer Gerhard
- Petritsch Peter
- Tscheliessnigg Karlheinz
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- Abstract:
- Cyclosporin A (CyA) is intensively metabolized by the hepatic cytochrome p450 III monooxygenase A system in the human liver, the most important metabolites being M1, M17, and M21. Because CyA and its metabolites have nephrotoxic, hepatotoxic, and neurotoxic side effects, CyA dosage must be calculated to avoid the risk of organ rejection through underdosage and toxic organ damage through overdosage or accumulation of metabolites. In this study, we determined the whole-blood concentrations of cyclosporin and metabolite M17 by high-pressure liquid chromatography (HPLC) and by monoclonal specific and polyclonal nonspecific fluorescence polarization immunoassay (Abbott) in patients after immunosuppressive treatment. Patients with different resorption and metabolization rates showed high individual variations. CyA concentrations in patients with good liver function and low concentrations of CyA metabolites showed a good correlation between the HPLC and the FPIA (TDx-monoclonal assay) methods in ranges between 25 and 180 ng/mL. TDx-monoclonal was not always as precise as HPLC. In cases of metabolic disorders, we found false high CyA concentrations assayed with the immunologic method, caused by a crossreaction of the elevated metabolite concentration. We found that HPLC rendered more information about the extent of immunosuppressive activity and the metabolization rate and showed a good correlation with the concentration of metabolite M17 and total metabolites measured with the Abbott CyA polyclonal kit.
- Find related publications in this database (using NLM MeSH Indexing)
- Antibodies - diagnostic use
- Antibodies, Monoclonal - diagnostic use
- Autoimmune Diseases - blood Autoimmune Diseases - drug therapy
- Bone Marrow Transplantation -
- Chromatography, High Pressure Liquid -
- Cross Reactions -
- Cyclosporine - administration & dosage Cyclosporine - adverse effects Cyclosporine - metabolism Cyclosporine - therapeutic use
- Cyclosporins - adverse effects Cyclosporins - blood
- Cytochrome P-450 Enzyme System - metabolism
- Fluorescence Polarization Immunoassay -
- Graft Rejection - prevention & control
- Heart Transplantation -
- Humans -
- Immunosuppression -
- Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - adverse effects Immunosuppressive Agents - metabolism Immunosuppressive Agents - therapeutic use
- Kidney - drug effects
- Kidney Transplantation -
- Liver - drug effects Liver - enzymology
- Liver Transplantation -
- Metabolic Clearance Rate -
- Nervous System - drug effects
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