生物学的同等性とバイオアベイラビリティのジャーナル

概要

Pharmacokinetics and Pharmacodynamics of Unfractionated Heparin and Ferric Pyrophosphate Citrate Co-administration during Hemodialysis: No DrugDrug Interaction

Raymond D Pratt

Background: Ferric Pyrophosphate Citrate (FPC) for intravenous administration is approved to maintain hemoglobin in patients receiving Chronic Hemodialysis (HD). The aim of this study is to investigate the coadministration of intravenous (IV) FPC with Unfractionated Heparin (UFH) as an admixture via the HD-machine syringe pump.

Methods: Open-label, randomized, 3-period crossover study. Three (3) treatments in randomized sequence: Treatment A: FPC 6.75 mg IV via the post dialyzer blood line and continuous infusion of UFH pre-dialyzer via the HD-machine infusion pump; Treatment B: FPC 6.75 mg IV mixed with UFH via the pre dialyzer heparin line; Treatment C; IV UFH via the on machine syringe pump x 3 h. anti-Xa activity, activated prothrombin time (aPTT), Thrombin time (TT) and serum iron parameters were measured. Pharmacokinetics and dynamics were determined using non-compartmental methods and comparisons of C_max and AUC were calculated using a standard bioequivalence approach.

Results: Mean anti-Xa, aPTT, and TT concentrations were comparable across all timepoints at baseline, and throughout the study. The concentration-time profiles for iron and TSAT were the same between the FPC/UFH admixture and FPC/UFH administered by separate routes. Results on the visual clotting scale were similar across all treatments. FPC and UFH were well tolerated with no reported adverse events.

Conclusion: No clinically relevant drug-drug interaction between FPC and UFH on the anticoagulation effects of UFH (as assessed by anti-Xa activity, aPTT, and TT) or on the ability of FPC to deliver iron when these agents are coadministered as a single admixture. No new safety concerns were identified.