Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound.
Drug Des Devel Ther
; 11: 3401-3412, 2017.
Article
em En
| MEDLINE
| ID: mdl-29238166
ABSTRACT
BACKGROUND:
Ferric carboxymaltose (FCM) is a stable, non-dextran-based intravenous iron complex used to treat iron deficiency of various etiologies. As FCM is a nonbiological complex drug and cannot be fully characterized by physicochemical analyses, it is important to demonstrate in nonclinical models that FCM similars (FCMS) have similar biodistribution. MATERIALS ANDMETHODS:
A total of 30 nonanemic rats were treated weekly with 40 mg iron/kg body weight intravenous FCM, FCMS, or isotonic saline (controls) for 4 weeks. Blood pressure, liver enzymes, and renal function were evaluated. In liver, heart, and kidney tissue, markers for oxidative stress (malondialdehyde to assess lipid peroxidation and antioxidant enzymes) and inflammation (TNFα and IL6) were measured. Iron deposits were localized.RESULTS:
The FCMS-treated group had significantly lower blood pressure, higher liver enzymes, increased proteinuria, and reduced creatinine clearance versus the FCM and control groups by day 29. Serum iron and transferrin saturation were significantly higher with FCMS versus FCM or controls. Iron deposition was altered in FCMS-treated animals, with decreased ferritin deposits and iron deposition outside the physiological storage compartments. Markers for lipid peroxidation and antioxidant-enzyme activity were significantly increased after FCMS administration versus FCM and controls, as were inflammatory markers.CONCLUSION:
Results from this blinded nonclinical study demonstrated significant differences between the originator FCM and this FCMS.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Férricos
/
Sistema Cardiovascular
/
Rim
/
Fígado
/
Maltose
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Drug Des Devel Ther
Assunto da revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Argentina