[The effect of ferric citrate hydrate as an iron replacement therapy in Japanese patients with iron deficiency anemia].

Patients with iron deficiency anemia (IDA) need to take oral iron preparations, which serve as the first-line treatment in IDA, for several months in order to replenish body iron stores after the improvement of anemia. However, existing oral iron preparations have concerns regarding its long-term use due to side effects, such as gastrointestinal symptoms. Previous clinical studies have shown that ferric citrate hydrate (FC) exhibits sufficient therapeutic efficacy in patients with IDA and lowers the risks of nausea and vomiting in comparison with existing oral iron preparations. In this study, we evaluated the efficacy and safety of FC administration at doses of 500 and 1,000 mg/day for up to 24 weeks as iron replacement therapy in patients with IDA. The results of this study showed that both the doses of FC improved anemia and iron-deficiency conditions and led to sufficient iron replacement response in most patients with IDA. No safety concerns were identified. Therefore, FC is expected to be a novel oral iron preparation for patients with IDA.

Efficacy and safety of ferric citrate hydrate compared with sodium ferrous citrate in Japanese patients with iron deficiency anemia: a randomized, double-blind, phase 3 non-inferiority study.

Oral iron preparations are used as first-line treatment for iron deficiency anemia (IDA), but their gastrointestinal side effects prevent patients from appropriate adherence. We recently conducted a randomized, double-blind, phase 3 non-inferiority study to evaluate the efficacy and safety of two dosages of ferric citrate hydrate (FC) compared with sodium ferrous citrate (SF) in patients with IDA. FC at both 500 and 1000 mg/day was non-inferior to SF at 100 mg/day in terms of the change in the hemoglobin concentration at Week 7 from baseline. Logistic regression analysis suggested that the cumulative proportion of patients who achieved the target hemoglobin concentration (≥ 13.0 g/dL in male patients and ≥ 12.0 g/dL in female patients) at Week 7 was highest among those treated with FC at 1000 mg/day, followed by SF at 100 mg/day and FC at 500 mg/day. Both dosages of FC were well tolerated in patients with IDA. The incidences of nausea and vomiting were significantly lower in the FC treatment groups than in the SF group. In conclusion, FC has potential to be an oral iron preparation with sufficient efficacy for the treatment of IDA and a lower risk of nausea and vomiting.

Randomised clinical trial of ferric citrate hydrate on anaemia management in haemodialysis patients with hyperphosphataemia: ASTRIO study.

Ferric citrate hydrate (FC) is an iron-based phosphate binder approved for hyperphosphataemia in patients with chronic kidney disease. We conducted a randomised controlled trial to evaluate the effects of FC on anaemia management in haemodialysis patients with hyperphosphataemia. We 1:1 randomised 93 patients who were undergoing haemodialysis and being treated with non-iron-based phosphate binders and erythropoiesis-stimulating agents (ESA) to receive 24 weeks of FC or to continue their non-iron-based phosphate binders (control) in a multicentre, open-label, parallel-design. Phosphate level was controlled within target range (3.5-6.0 mg/dL). The primary endpoint was change in ESA dose from baseline to end of treatment. Secondary endpoints were changes in red blood cell, iron and mineral, and bone-related parameters. Compared with control, FC reduced ESA dose [mean change (SD), -1211.8 (3609.5) versus +1195 (6662.8) IU/week; P = 0.03] without significant differences in haemoglobin. FC decreased red blood cell distribution width (RDW) compared with control. While there were no changes in serum phosphate, FC reduced C-terminal fibroblast growth factor (FGF) 23 compared with control. The incidence of adverse events did not differ significantly between groups. Despite unchanged phosphate and haemoglobin levels, FC reduced ESA dose, RDW, and C-terminal FGF23 compared with control.

A hepatocarcinogenic tryptophan-pyrolyzate component, Trp-P-1, decreases serum total testosterone level and induces hepatic Cyp1a2 in male mice.

Male (BALB/c x DBA/2) F(1) mice were given 3-amino-1,4-dimethyl-5H-pyrido [4,3-b] indole acetate (Trp-P-1; 20 mg/kg body weight) by gavage at 24-h intervals for 1 or 2 weeks, and the effects of Trp-P-1 on the levels of serum total testosterone and hepatic cytochrome P4501a2 (Cyp1a2) were examined. A significant decrease in serum total testosterone level was observed after treatment with Trp-P-1 for 2 weeks, but not for 1 week. Likewise, gene expression levels of testicular androgenic enzymes, including cholesterol side chain cleavage cytochrome P450, 3beta-hydroxysteroid dehydrogenase and steroid 17alpha-hydroxylase/C17-20 lyase, decreased only in the mice treated with Trp-P-1 for 2 weeks. In contrast, levels of the mRNA and apoprotein of hepatic Cyp1a2 and its enzyme activity for O-demethylation of methoxyresorufin significantly increased in the mice treated with Trp-P-1 for 2 weeks, but only a small increase was observed in mice treated for 1 week. In the present study, we demonstrate for the first time that treatment of male mice with Trp-P-1 results in a decrease in serum total testosterone level through suppression of the gene expression of testicular enzymes responsible for androgen biosynthesis, and this then leads to induction of hepatic Cyp1a2.