Low ‐volume LC–MS/MS method for the pharmacokinetic investigation of carvedilol, enalapril and their metabolites in whole blood and plasma: Application to a paediatric clinical trial

Evidence ‐based pharmacotherapy for treatment of paediatric heart failure is lacking due to very limited pharmacokinetic data. Therefore, a low‐volume LC–MS/MS assay was developed, validated and applied to determine enalapril, carvedilol and their metabolites using whole blood or plasma. The establishe d assay enables to generate reliable data of maturation‐dependent metabolism of the drugs and contributes to the implementation of evidence‐based pharmacotherapy in this vulnerable collective. AbstractEvidence ‐based pharmacotherapy with carvedilol and enalapril in children suffering from heart failure is insufficient owing to limited pharmacokinetic data. Although a few data sets regarding enalapril, its metabolite enalaprilat and carvedilol in children have been published, pharmacokinetic data on carv edilol metabolites are missing. However, for both drug substances, their active metabolites contribute substantially to drug efficacy. As data can hardly be derived from adults owing to the unknown impacts of enzymatic maturation and ontogeny during childhood, customised assays are important to faci litate paediatric evidence‐based pharmacotherapy. Considering ethical paediatric constraints, a low‐volume liquid chromatography coupled to mass spectrometry (LC–MS/MS) assay was developed using whole blood or plasma for the quantification of enalapril, enalaprilat, carvedilol, O‐desmethyl c arvedilol, 4‐ and 5‐hydroxyphenyl carvedilol as well as 3‐ and 8‐...
Source: Drug Testing and Analysis - Category: Drugs & Pharmacology Authors: Tags: RESEARCH ARTICLE Source Type: research