Iron Pharmacokinetics in Women with Iron Deficiency Anaemia Following A Single Oral Dose of a Novel Formulation of Tardyferon (Prolonged Release Ferrous Sulphate)

Abstract

Numerous iron-containing preparations are available on the market; these vary in dosage, salt, chemical state of iron (ferric or ferrous) and in the iron delivery process (immediate or prolonged-release). Tardyferon® is a prolonged-release tablet containing 80 mg ferrous sulphate. The formulation has recently been modified; changes to the excipients which constitute the inert formulation matrix have allowed a decrease in tablet size for easier swallowing. The aim of this multicenter open-label study was to characterize the serum pharmacokinetics of iron in non-pregnant women aged 23–45 years with iron deficiency anaemia (IDA) following single oral administration of 160 mg Tardyferon® under fasting conditions. Blood samples were collected from the 29 participants before dosing and until 24 h post-dosing. Serum iron concentrations were determined using a routine colorimetric analytical method; pharmacokinetic parameters were derived using a non-compartmental approach. In these patients, median time to maximum serum concentrations (Tmax) was 4 h. Serum profiles were consistent with prolonged release; iron levels were elevated up to 12 h after dosing, with mean C_12h still more than 7 times higher than baseline (C_T0), and mean C_2h and C_8h representing 69.7% and 81.9% of the C_max, respectively. In vitro dissolution testing performed on the clinical batch also demonstrated prolonged release of iron from this formulation. A single oral dose of 160 mg Tardyferon® administered under fasting conditions to this target population resulted in a long-lasting release of iron in the gastrointestinal tract, leading to optimal iron absorption. Moreover, Tardyferon® was well tolerated.

Key words

Iron deficiency - absorption - bioavailability - drug delivery

• References

• 1 McLean E, Cogswell M, Egli I. et al. Worldwide prevalence of anaemia, WHO vitamin and mineral nutrition information system, 1993-2005. Public Health Nutrition 2008; 12: 444-454
• 2 Beard JL. Effectiveness and strategies of iron supplementation during pregnancy. Am J Clin Nutr 2000; 71 suppl 1288S-1294S
• 3 WHO. Serum ferritin concentrations for the assessment of iron status and iron deficiency in population. Vitamin and Nutrition Information System. Geneva. World Health Organization 2011(WHO/NMH/NHD/MNM/11.2) WHO. Iron deficiency anaemia: Assessment, prevention and control. World Health Organization 2001: 1-114
• 4 Camaschella C. Iron-Deficiency Anaemia. New England Journal of Medicine 2015; 372: 1832-1843
• 5 Lopez A, Cacoub P, Macdougall IC. et al. Iron deficiency anaemia. Lancet 2016; 387: 907-916
• 6 Palacios S. Ferrous versus ferric oral iron formulation for the treatment of iron deficiency: A clinical overview. The Scientific World Journal 2012; article ID 846824: 5 10.1100/2012/846824
• 7 Berber I, Diri H, Erkurt MA. et al. Evaluation of ferric and ferrous iron therapies in women with iron deficiency anaemia. Adv Hematol 2014; 2014: 297057 10.1155/2014/297057
• 8 Baird IM, Walters RL, Sutton DR. Absorption of slow-release iron and effects of ascorbic acid in normal subjects and after partial gastrectomy. Br Med J 1974; 4: 505-508
• 9 Cancelo-Hidalgo MJ, Castelo-Branco C, Palacios S. et al. Tolerability of different oral iron supplements: A systematic review. Curr Med Res Opin. 2013; 29: 291-303
• 10 Leary A, Barthe L, Clavel T. et al. Pharmacokinetics of ferrous sulphate (tardyferon®) after single oral dose administration in women with iron deficiency anaemia. Drug Res 2015; 66: 51-56
• 11 Zaim M, Piselli L, Fioravanti P. et al. Efficacy and tolerability of a prolonged release ferrous sulphate formulation in iron deficiency anaemia: a non- inferiority controlled trial. Eur J Nutr 2012; 51: 221-229
• 12 Siedel J, Wahlefeld AW, Zieggenhorn J. Improved FerrozineR-based reagent for the determination of serum iron (Transferin iron) without deproteinization. Clin Chem 1984; 30: 975 (AACC-Meeting Abstract)
• 13 Wheby MS. Site of iron absorption in man. Scand J Haematol 1970; 7: 56-62