Abstract: SA-PO654

Single Ascending Dose Study of Intraperitoneal Triferic® (Ferric Pyrophosphate Citrate) in Patients on Chronic Peritoneal Dialysis

Session Information

Category: Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics

  • 1601 Pharmacokinetics, Pharmacodynamics, Pharmacogenomics

Authors

  • Pratt, Raymond D., Rockwell Medical Inc, Wixom, Michigan, United States
  • Grimberg, Sarah L, Rockwell Medical, Inc., Mission Viejo, California, United States
  • Gupta, Ajay, Rockwell Medical Inc, Wixom, Michigan, United States
Background

The inconvenience of giving intravenous (IV) iron as an outpatient has limited its use in peritoneal dialysis patients (PD). Ferric pyrophosphate citrate (FPC) is a complex, water soluble iron salt approved to maintain iron balance and hemoglobin in patients receiving chronic hemodialysis. FPC donates iron to transferrin, bypassing the reticuloendothelial block to iron metabolism in patients with chronic kidney disease. We postulated that FPC could be administered in peritoneal dialysis fluid (PDF) to replace and/or maintain iron stores.

Methods

Thirty (30) PD patients were enrolled in an open-label, randomized, two-period, single ascending dose study of FPC administered in PDF in 5 cohorts. All patients received FPC in either Dianeal® (1.5% or 2.5% dextrose) 2 L or Extraneal® (Icodextrin 7.5%) 1.5 L for a 12 hour dwell. FPC was added to the PDF at iron concentrations of 2.5, 5.0 (2 cohorts), 7.5, or 12.5 mg Fe/L. At another session, 6.6 mg FPC was administered IV over 4 hours. A serum iron profile (sFe) was obtained at defined time points to characterize the PK of absorbed iron.

Results

Iron absorption from PDF was dose dependent with peak sFe values at approximately 6 hours. Clearance of PD administered iron followed the time course of IV FPC administration. Serum iron levels exhibited an initial rapid rise followed by a slower increase. Estimates of iron absorption ranged from 0.8 mg with the 2.5 mg Fe/L dose to 7.3 mg Fe with the 12.5 mg Fe/L dose.
Triferic was generally well tolerated. Two patients (7%) experienced moderate abdominal discomfort and cramping upon infusion of the 12.5 and 7.5 mg dose. One subject in the 12.5 mg dose group withdrew due to the event the other event resolved. Transient nausea and vomiting were experienced by 2 patients (7%) upon infusion of PDF. No changes in PDF cell counts or differential were observed at any dose level.

Conclusion

Ferric pyrophosphate citrate (Triferic®) iron is bioavailable via peritoneal dialysis. The adverse effects were mild to moderate in severity and appeared to be dose dependent. Iron absorbed from PDF to the systemic circulation was rapidly cleared with a time course similar to IV FPC. FPC added to PDF may be an effective and simple iron replacement therapy for PD patients.

Funding

  • Commercial Support