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

    loading  Checking for direct PDF access through Ovid


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.HighlightsA novel preclinical model based on turkey embryos is introduced to evaluate disposition of complex iron products.The model may beutilized to study expected bioequivalence between different iron complex formulations.Dose dependence of iron accumulation in liver, kidney and heart is shown.The model is available for the characterization of Non-biological complex drugs (NBCD).

    loading  Loading Related Articles