Serum concentrations of levosimendan and its metabolites OR-1855 and OR-1896 in cardiac surgery patients with cardiopulmonary bypass
BackgroundThe inotropic drug levosimendan is often used as an individualized therapeutic approach perioperatively in cardiac surgery patients with cardiopulmonary bypass (CPB). Data regarding serum concentrations of levosimendan and its metabolites within this context is lacking.MethodsIn this retro...
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Frontiers Media S.A.
2024-08-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2024.1406338/full |
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| author | Hannah Kipka Hannah Kipka Uwe Liebchen Max Hübner Max Hübner Georg Höfner Otto Frey Klaus T. Wanner Erich Kilger Christian Hagl Christian Hagl Roland Tomasi Hanna Mannell Hanna Mannell Hanna Mannell |
| author_facet | Hannah Kipka Hannah Kipka Uwe Liebchen Max Hübner Max Hübner Georg Höfner Otto Frey Klaus T. Wanner Erich Kilger Christian Hagl Christian Hagl Roland Tomasi Hanna Mannell Hanna Mannell Hanna Mannell |
| author_sort | Hannah Kipka |
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| description | BackgroundThe inotropic drug levosimendan is often used as an individualized therapeutic approach perioperatively in cardiac surgery patients with cardiopulmonary bypass (CPB). Data regarding serum concentrations of levosimendan and its metabolites within this context is lacking.MethodsIn this retrospective descriptive proof-of-concept study, total serum concentrations (TSC) and unbound fractions (UF) of levosimendan and its metabolites OR-1896 and OR-1855 in cardiac surgery patients with CPB were measured using LC-ESI-MS/MS. Simulation of expected levosimendan TSC was performed using Pharkin 4.0. Serum NT-proBNP was assessed with ELISA.ResultsAfter levosimendan infusion (1.25 mg or 2.5 mg, respectively) after anaesthesia induction, a median TSC of 1.9 ng/ml and 10.4 ng/ml was determined in samples taken directly after surgery (T1). Median TSC of 7.6 ng/ml and 22.0 ng/ml, respectively, were simulated at T1. Whereas 1.1 ng/ml and 1.6 ng/ml TSC of OR-1896, respectively, was quantified the day after surgery (T2), TSC of the intermediate metabolite OR-1855 was mostly below the lower limit of quantification (LLOQ). The UF was 0.5% and 1.1% for levosimendan and 64.1% and 52.1% for OR-1896, respectively, with over half the samples being below LLOQ. NT-proBNP concentrations before surgery and T2 did not differ.DiscussionThe low TSC, UF and unchanged NT-proBNP levels in combination with high variation of serum levels between patients suggest a need for optimized dosing regimen of levosimendan combined with therapeutic drug monitoring for such an individualized approach. In addition, the differences between the measured and estimated concentrations may suggest a possible influence of CPB on levosimendan serum concentrations. |
| format | Article |
| id | doaj-art-11983f42dde040bb85cd8b99de014085 |
| institution | Kabale University |
| issn | 2297-055X |
| language | English |
| publishDate | 2024-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj-art-11983f42dde040bb85cd8b99de0140852024-11-22T11:36:45ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2024-08-011110.3389/fcvm.2024.14063381406338Serum concentrations of levosimendan and its metabolites OR-1855 and OR-1896 in cardiac surgery patients with cardiopulmonary bypassHannah Kipka0Hannah Kipka1Uwe Liebchen2Max Hübner3Max Hübner4Georg Höfner5Otto Frey6Klaus T. Wanner7Erich Kilger8Christian Hagl9Christian Hagl10Roland Tomasi11Hanna Mannell12Hanna Mannell13Hanna Mannell14Doctoral Program Clinical Pharmacy, LMU University Hospital, LMU Munich, GermanyInstitute of Cardiovascular Physiology and Pathophysiology, Biomedical Center, LMU Munich, Planegg, GermanyDepartment of Anaesthesiology, LMU University Hospital, LMU Munich, Munich, GermanyDepartment of Anaesthesiology, LMU University Hospital, LMU Munich, Munich, GermanyWalter Brendel Center of Experimental Medicine, LMU Munich, LMU University Hospital, Munich, GermanyDepartment of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, GermanyDepartment of Pharmacy, General Hospital of Heidenheim, Heidenheim, GermanyDepartment of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, GermanyDepartment of Anaesthesiology, LMU University Hospital, LMU Munich, Munich, GermanyDepartment of Cardiac Surgery, LMU University Hospital, LMU Munich, GermanyDZHK (German Centre of Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, GermanyDepartment of Anaesthesiology, LMU University Hospital, LMU Munich, Munich, GermanyDoctoral Program Clinical Pharmacy, LMU University Hospital, LMU Munich, GermanyInstitute of Cardiovascular Physiology and Pathophysiology, Biomedical Center, LMU Munich, Planegg, GermanyPhysiology, Institute for Theoretical Medicine, Faculty of Medicine, University of Augsburg, Augsburg, GermanyBackgroundThe inotropic drug levosimendan is often used as an individualized therapeutic approach perioperatively in cardiac surgery patients with cardiopulmonary bypass (CPB). Data regarding serum concentrations of levosimendan and its metabolites within this context is lacking.MethodsIn this retrospective descriptive proof-of-concept study, total serum concentrations (TSC) and unbound fractions (UF) of levosimendan and its metabolites OR-1896 and OR-1855 in cardiac surgery patients with CPB were measured using LC-ESI-MS/MS. Simulation of expected levosimendan TSC was performed using Pharkin 4.0. Serum NT-proBNP was assessed with ELISA.ResultsAfter levosimendan infusion (1.25 mg or 2.5 mg, respectively) after anaesthesia induction, a median TSC of 1.9 ng/ml and 10.4 ng/ml was determined in samples taken directly after surgery (T1). Median TSC of 7.6 ng/ml and 22.0 ng/ml, respectively, were simulated at T1. Whereas 1.1 ng/ml and 1.6 ng/ml TSC of OR-1896, respectively, was quantified the day after surgery (T2), TSC of the intermediate metabolite OR-1855 was mostly below the lower limit of quantification (LLOQ). The UF was 0.5% and 1.1% for levosimendan and 64.1% and 52.1% for OR-1896, respectively, with over half the samples being below LLOQ. NT-proBNP concentrations before surgery and T2 did not differ.DiscussionThe low TSC, UF and unchanged NT-proBNP levels in combination with high variation of serum levels between patients suggest a need for optimized dosing regimen of levosimendan combined with therapeutic drug monitoring for such an individualized approach. In addition, the differences between the measured and estimated concentrations may suggest a possible influence of CPB on levosimendan serum concentrations.https://www.frontiersin.org/articles/10.3389/fcvm.2024.1406338/fulllevosimendanOR-1896OR-1855cardiac insufficiencycardiopulmonary bypassserum levels |
| spellingShingle | Hannah Kipka Hannah Kipka Uwe Liebchen Max Hübner Max Hübner Georg Höfner Otto Frey Klaus T. Wanner Erich Kilger Christian Hagl Christian Hagl Roland Tomasi Hanna Mannell Hanna Mannell Hanna Mannell Serum concentrations of levosimendan and its metabolites OR-1855 and OR-1896 in cardiac surgery patients with cardiopulmonary bypass Frontiers in Cardiovascular Medicine levosimendan OR-1896 OR-1855 cardiac insufficiency cardiopulmonary bypass serum levels |
| title | Serum concentrations of levosimendan and its metabolites OR-1855 and OR-1896 in cardiac surgery patients with cardiopulmonary bypass |
| title_full | Serum concentrations of levosimendan and its metabolites OR-1855 and OR-1896 in cardiac surgery patients with cardiopulmonary bypass |
| title_fullStr | Serum concentrations of levosimendan and its metabolites OR-1855 and OR-1896 in cardiac surgery patients with cardiopulmonary bypass |
| title_full_unstemmed | Serum concentrations of levosimendan and its metabolites OR-1855 and OR-1896 in cardiac surgery patients with cardiopulmonary bypass |
| title_short | Serum concentrations of levosimendan and its metabolites OR-1855 and OR-1896 in cardiac surgery patients with cardiopulmonary bypass |
| title_sort | serum concentrations of levosimendan and its metabolites or 1855 and or 1896 in cardiac surgery patients with cardiopulmonary bypass |
| topic | levosimendan OR-1896 OR-1855 cardiac insufficiency cardiopulmonary bypass serum levels |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2024.1406338/full |
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