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Bioanalysis ; 5(1): 53-63, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23256472

ABSTRACT

BACKGROUND: Microdosing is a technique for studying the behavior of compounds in vivo at 1/100th of the dose of a test substance calculated, based on animal data, to yield a pharmacologic effect. In microdosing, use is made of accelerator MS (AMS). In this study, we investigated whether (129)I-labeling of proteins with subsequent AMS measurements is a suitable method to perform microdose studies with therapeutic proteins. We used erythropoietin (EPO) as a case study. RESULTS: In an animal study with (129)I-labeled EPO in Han-Wistar rats, an increase of (129)I-EPO is observed after dose administration. The half-life was found to be 2 and 5.5 h for two different EPOs. These results are in accordance with expected values. CONCLUSION: Although further research is required, (129)I-labeling of proteins seems a feasible method for AMS microdose studies with peptide and protein drugs, such as biosimilars.


Subject(s)
Drug Discovery/methods , Erythropoietin/blood , Mass Spectrometry , Acceleration , Animals , Chromatography, Liquid , Dose-Response Relationship, Drug , Erythropoietin/administration & dosage , Erythropoietin/chemistry , Erythropoietin/pharmacokinetics , Feasibility Studies , Half-Life , Humans , Iodine Isotopes/blood , Iodine Isotopes/chemistry , Male , Rats , Rats, Wistar , Surface Plasmon Resonance
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