Abstract
BACKGROUND AND OBJECTIVE: Anemia caused by iron depletion is common in patients with hemodialysis-dependent stage 5 chronic kidney disease (CKD-5HD) patients. To maintain the iron levels, external administration of iron is essential. Ferric pyrophosphate citrate (FPC) is a novel, water-soluble complex iron salt. The present study was conducted to evaluate the pharmacokinetic (PK) parameters and safety of FPC in adult healthy Chinese subjects and patients with CKD-5HD. METHODS: Two open-label, single-center studies were conducted in healthy subjects and patients with CKD-5HD. Healthy subjects received a single intravenous dose of 6.5 mg FPC solution, while CKD-5HD patients were randomized to two different sequences of FPC administration at two sequential hemodialysis (HD) treatments (dose 1 and dose 2). Patients received 27.2 mg of FPC at a dialysate concentration of 95 μg/L for 4 h or a single 6.5 mg dose of FPC administered intravenously via the pre-dialyzer blood circuit. The primary objective was to determine the PK parameters of total serum iron (Fe(tot)), while the secondary objective was the safety of the FPC solution. PK parameters were calculated using Phoenix WinNonlin 8.1 and other parameters were analyzed using SAS 9.4 software. Comparison between HD dose 2 and HD dose 1 was performed using the Wilcoxon rank-sum test and analysis of variance (ANOVA). RESULTS: A total of 14 healthy subjects with a mean age of 30.8 ± 5.92 years and 12 HD patients with a mean age of 54.3 ± 16.47 years were included. In healthy subjects, the peak serum concentration was reached at the end of infusion of FPC, with an adjusted mean maximum concentration (C(max,)) of 33.46 ± 4.83 μmol/L at a mean time to reach C(max) (T(max)) of 4.09 ± 0.19 h. In patients with CKD-5HD, the adjusted mean C(max) of HD dose 2 was 25.37 ± 4.30 μmol/L at a T(max,) of 3.09 ± 0.32 h, whereas the C(max,) of HD dose 1 was 24.59 ± 4.77 μmol/L at a T(max,) of 3.96 ± 0.26 h. The Fe(tot) concentration-time curves were observed to be similar for both administration methods (HD doses 1 and 2), while the PK parameters differed significantly for T(max) (p = 0.001; baseline correction) and area under the concentration-time curve from time zero to time t (AUC(t)) [p = 0.031 for cycle variance; without baseline correction] between HD doses 1 and 2. The geometric mean ratios (HD dose 1/HD dose 2) for C(max) and AUC(t) were within the 85-125% range (C(max) 96.56%; AUC(t) 96.07%). A total of three and two incidences of adverse events were reported in healthy subjects and patients with CKD-5HD, respectively. CONCLUSION: FPC showed a good PK and safety profile and hence can be used as maintenance therapy for patients with CKD-5HD by choosing a better method of administration based on clinical feasibility and requirement. CLINICAL TRIAL REGISTRATION: CTR20181113 and CTR20181119.