title: Differences in tissue distribution of iron from various clinically used intravenous iron complexes in fetal avian heart and liver.
abstract: Nanomedicines are more complex than most pharmacologically active substances or medicines and have been considered as non-biological complex drugs. For nanomedicines pivotal pharmacokinetic properties cannot be assessed by plasma concentration data from standard bioequivalence studies. Using intravenous iron complexes (IICs) as model we show that fetal avian tissues can be used to study time dependent tissue concentrations in heart and liver. Clear differences were found between equimolar doses of sucrose, gluconate or carboxymaltose coated iron particles. The range in tissue iron concentrations observed with these clinically widely used IICs provides an orientation as to what should be acceptable for any new IICs. Moreover, sensitivity of the experimental model was high enough to detect a 20% difference in tissue iron concentration. For the authorization of generic products under Article 10 (1) of Directive 2001/83/EC a plasma concentration of an active substance in the range of 80%-125% versus the reference product is usually considered acceptable. Based on its high discriminatory sensitivity this method was used to support a positive marketing authorization decision for a generic nanomedicine product.
authors.affiliation: Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Spicher
authors.affiliation: Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Brendler-Schwaab
authors.affiliation: Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schlösser
authors.affiliation: Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Catarinolo
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Fütterer
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Langguth
authors.affiliation: Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany. Electronic address: Harald.enzmann@bfarm.de.
authors.forename: Harald
authors.initials: H
authors.lastname: Enzmann
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D002645:Chickens / Q000378:metabolism*; D016568:Drugs, Generic / Q000008:administration & dosage / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D007501:Iron / Q000008:administration & dosage / Q000378:metabolism*; D058085:Iron Compounds / Q000008:administration & dosage / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D050997:Nanomedicine / Q000379:methods; D013810:Therapeutic Equivalency; D014018:Tissue Distribution / Q000502:physiology*
chemical_list: D016568:Drugs, Generic; D058085:Iron Compounds; D007501:Iron
keywords: Bioequivalence; Essential similarity; Generic medicine; Iron; Nanomedicine; Non-biological complex drugs; Organotropy; Tissue distribution