From Therapeutic Drug Monitoring To Drug Management: IMPDH Activity As Novel Surrogate Marker For Dose Adjustment Of Mycophenolate In Immunosuppressive Therapy
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| Natura: | Recurso digital |
| Lingua: | inglese |
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1970
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| _version_ | 1866901443338829824 |
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| author | Manfred Küpper Rana Hallak |
| author_facet | Manfred Küpper Rana Hallak |
| contents | Background: Mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (ECMPS) are well established in immunosuppressive therapy after renal transplantation. The active substance, mycophenolic acid, leads to an inhibition of inosine-monophosphate-dehydrogenase (IMPDH) activity in peripheral mononuclear cells. Adverse side effects, most prominently gastrointestinal (GIT) side effects, lead to dose reduction in more than half of the patients, increasing the risk for acute rejection. Therapeutic drug monitoring (TDM) by measuring the trough level shows no relevant correlations with MPA-AUC values, and is consequently obsolete for assessing the risk of graft loss. Therefore the residual IMPDH activity in stable maintenance renal transplant patients was determined in order to suggest trusted intervals allowing monitoring of the level of immunosuppression in the context of dose-reduction. In order to compare the efficacy of the two galenisms, MMF and EC-MPS, respectively, the effect of different dosing patterns of MMF and EC-MPS on IMPDH activity in stable patients after renal transplantation was analyzed. Materials and Methods: IMPDH activity (pmol/s per pmol AMP) was measured in patients in the maintenance phase after renal transplantation. Besides MMF or EC-MPS, immunosuppressive therapy consisted of calcineurin inhibitor with or without steroids. From 276 maintenance renal transplant patients 2432 individual trough levels and 73 kinetics were obtained for delineation of trusted intervals; for comparing the efficacy of the two galenisms, 260 measurements in 110 patients (82 on MMF, and 28 on EC-MPS) were<br><br>This version is archived in the Arab International University (AIU) repository for open access and dissemination purposes. The content of this paper has not been modified from the original publication.<br>For more information, please visit the official repository of <b>Arab International University (AIU)</b>:<br><br><a href="https://aiu.edu.sy">https://aiu.edu.sy</a> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_19764402 |
| institution | Zenodo |
| language | eng |
| publishDate | 1970 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | From Therapeutic Drug Monitoring To Drug Management: IMPDH Activity As Novel Surrogate Marker For Dose Adjustment Of Mycophenolate In Immunosuppressive Therapy Manfred Küpper Rana Hallak Background: Mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (ECMPS) are well established in immunosuppressive therapy after renal transplantation. The active substance, mycophenolic acid, leads to an inhibition of inosine-monophosphate-dehydrogenase (IMPDH) activity in peripheral mononuclear cells. Adverse side effects, most prominently gastrointestinal (GIT) side effects, lead to dose reduction in more than half of the patients, increasing the risk for acute rejection. Therapeutic drug monitoring (TDM) by measuring the trough level shows no relevant correlations with MPA-AUC values, and is consequently obsolete for assessing the risk of graft loss. Therefore the residual IMPDH activity in stable maintenance renal transplant patients was determined in order to suggest trusted intervals allowing monitoring of the level of immunosuppression in the context of dose-reduction. In order to compare the efficacy of the two galenisms, MMF and EC-MPS, respectively, the effect of different dosing patterns of MMF and EC-MPS on IMPDH activity in stable patients after renal transplantation was analyzed. Materials and Methods: IMPDH activity (pmol/s per pmol AMP) was measured in patients in the maintenance phase after renal transplantation. Besides MMF or EC-MPS, immunosuppressive therapy consisted of calcineurin inhibitor with or without steroids. From 276 maintenance renal transplant patients 2432 individual trough levels and 73 kinetics were obtained for delineation of trusted intervals; for comparing the efficacy of the two galenisms, 260 measurements in 110 patients (82 on MMF, and 28 on EC-MPS) were<br><br>This version is archived in the Arab International University (AIU) repository for open access and dissemination purposes. The content of this paper has not been modified from the original publication.<br>For more information, please visit the official repository of <b>Arab International University (AIU)</b>:<br><br><a href="https://aiu.edu.sy">https://aiu.edu.sy</a> |
| title | From Therapeutic Drug Monitoring To Drug Management: IMPDH Activity As Novel Surrogate Marker For Dose Adjustment Of Mycophenolate In Immunosuppressive Therapy |
| url | https://doi.org/10.5281/zenodo.19764402 |