Iron-deficiency anemia (IDA) is the most common form of anemia. Iron replacement therapy is an effective treatment, but oral and previously available intravenous (IV) formulations in Japan have disadvantages such as side effects, immunogenic reactions, low dose per tablet/vial, and the need for continuous administration. Ferric carboxymaltose (FCM), which overcomes these limitations, is widely used as an IV iron preparation outside of Japan. In this single-center, open-label, single-dose escalation study, we investigated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of FCM in Japanese subjects. Twenty-four Japanese IDA patients, diagnosed by hemoglobin, serum ferritin, and transferrin saturation, were assigned in equal groups to the 100, 500, 800, and 1000 mg iron dose arms. All subjects completed the study without important protocol deviations. Mean total serum iron concentrations showed a rapid, dose-dependent increase after FCM injection, reaching a maximum within 1 h. Mean reticulocyte counts significantly increased in all arms, suggesting improved hematopoietic function. Fourteen of 24 subjects experienced adverse events, but these were neither serious nor led to drug interruption. The PK/PD and safety profiles were similar in Japanese and European subjects. Ferric carboxymaltose is safe for administration in Japanese patients with IDA.
PK/PD Ferric carboxymaltose Japanese Iron deficiency anemia (IDA)
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The authors are grateful to the patients and their families for their contributions. We would like to thank A. Urae for collaboration on this work.
Compliance with ethical standards
Conflict of interest
The present study was performed as phase Ib study funded by Zeria Pharmaceutical Co., Ltd. Katsuya Ikuta is involved in this study as a medical expert. Asami Shimura, Masaru Terauchi, Kazuyoshi Yoshii and Yoshihiro Kawabata are an employees of Zeria Pharmaceutical Co., Ltd.
Supplementary material 2 (JPEG 105 kb) Supplemental Fig. 1 Line chart of the mean TSAT between 1 day prior to FCM administration and 168 h after administration. Mean TSAT was increased rapidly after administration and reached almost 100% at 500, 800 and 1000 mg iron dose arms. At 100 mg iron dose arm, mean TSAT increased once up to 42.55% immediately after administration, and continued to increase gradually to reach a maximum at 24 h. ●: 100 mg iron, ○: 500 mg iron, △: 800 mg iron, ◊: 1000 mg iron
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