Randomized Open-Label Phase 1 Study of the Pharmacokinetics of Ferric Maltol in Inflammatory Bowel Disease Patients with Iron Deficiency

Eur J Drug Metab Pharmacokinet. 2017 Apr;42(2):229-238. doi: 10.1007/s13318-016-0334-5.

Abstract

Background: Iron deficiency anemia (IDA) is a common complication of inflammatory bowel disease (IBD). Oral ferric maltol improves and normalizes hemoglobin (Hb) in patients with IBD.

Aim: This open-label, randomized Phase 1 study evaluated the pharmacokinetics of ferric maltol and its effect on iron indices in IBD patients with iron deficiency (with or without anemia).

Methods: Iron deficient adult IBD patients received ferric maltol 30, 60, or 90 mg twice daily during an 8-day period. Pharmacokinetics and iron uptake were assessed on days 1 and 8.

Results: Twenty-four patients were included: 13 with Crohn's disease and 11 with ulcerative colitis (mean age 39 years; 67 % female, mean Hb 13.0 g/dL; mean reticulocyte Hb content (CHr) 31.9 pg; mean ferritin 13.9 µg/L). Plasma maltol and maltol glucuronide increased rapidly at all doses, reaching maximum plasma concentration (C max) 1.0-1.5 h post-dose and declining to baseline after 3-6 h. Maltol and maltol glucuronide exposure (area under the concentration-time curve; AUC) appeared dose proportional with twice-daily dosing, with higher exposure to maltol glucuronide vs. maltol. Mean day 8/day 1 ratios for C max and AUC0-t indicated no accumulation after 7 days of twice-daily dosing. Serum iron and transferrin saturation (TSAT) increased with all doses (maximum values at 1.5-3.0 h post-dose). Serum ferritin and CHr increased by day 8, with greater improvements with 60 and 90 mg twice-daily doses than with 30 mg twice-daily doses.

Conclusions: The key constituents of ferric maltol showed predictable pharmacokinetics, with no accumulation over 7 days and increased iron uptake and storage over time at 30-90 mg twice-daily doses.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anemia, Iron-Deficiency / drug therapy*
  • Anemia, Iron-Deficiency / etiology
  • Area Under Curve
  • Colitis, Ulcerative / complications*
  • Crohn Disease / complications*
  • Dose-Response Relationship, Drug
  • Female
  • Ferric Compounds / administration & dosage
  • Ferric Compounds / pharmacokinetics*
  • Glucuronides / pharmacokinetics
  • Hemoglobins / metabolism
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Pyrones / administration & dosage
  • Pyrones / pharmacokinetics*
  • Time Factors
  • Young Adult

Substances

  • Ferric Compounds
  • Glucuronides
  • Hemoglobins
  • Pyrones
  • ferric maltol