6533b81ffe1ef96bd127879d

RESEARCH PRODUCT

Bioequivalence decision for nanoparticular iron complex drugs for parenteral administration based on their disposition

Sören FüttererChristoph SchlösserKarsten SpicherMaria CatarinoloJulia SchnorrHarald EnzmannPeter Langguth

subject

0301 basic medicineEmbryo NonmammalianTissue concentrationsTurkeyAmylopectinDose dependenceBioequivalencePharmacologyKidneyToxicologyFerric CompoundsGlucaric Acid03 medical and health sciences0302 clinical medicinePharmacokineticsAnimalsDistribution (pharmacology)MedicineIron complexMaltoseFerric Oxide Saccharatedbusiness.industryMyocardiumGeneral MedicineDisposition030104 developmental biologyLiverTherapeutic Equivalency030220 oncology & carcinogenesisModels AnimalNanoparticlesIron-Dextran ComplexbusinessParenteral iron

description

Although parenteral iron products have been established to medicinal use decades before, their structure and pharmacokinetic properties are not fully characterized yet. With its' second reflection paper on intravenous iron-based nano-colloidal products (EMA/CHMP/SWP/620008/2012) the European Medicine Agency provided an extensive catalogue of methods for quality, non-clinical and pharmacokinetic studies for the comparison of nano-sized iron products to an originator (EMA, 2015). For iron distribution studies, the reflection paper assumed the use of rodents. In our tests, we used a turkey fetus model to investigate time dependent tissue concentrations in pharmacological and toxicological relevant tissues liver, heart and kidney. We found turkey embryos to be a suitable alternative to rodents with high discriminatory sensitivity. Clear differences were found between equimolar doses of iron products with hydroxyethyl amylopectin, sucrose, dextrane and carboxymaltose shell. A linear dose dependency for the tissue accumulation was also demonstrated.

yearjournalcountryeditionlanguage
2017-05-12Regulatory Toxicology and Pharmacology
https://doi.org/10.1016/j.yrtph.2018.02.009