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Abstract: SA-PO636

C-PAM, a Novel Iron Oxide-based Oral Drug, Efficiently Lowers Serum PI

Session Information

  • Pharmacology
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1700 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Wagner, Susanne E., Wagner MSL Management, Mahlow, Germany
  • Schnorr, Jörg, Charité - Universitätsmedizin Berlin, Berlin, Germany
  • Ebert, Monika, Charité - Universitätsmedizin Berlin, Berlin, Germany
  • Stolzenburg, Nicola, Charité - Universitätsmedizin Berlin, Berlin, Germany
  • Taupitz, Matthias, Charité - Universitätsmedizin Berlin, Berlin, Germany
Background

C-PAM is a novel compound designed for use as a serum Pi-lowering oral drug. It is composed of iron (Fe) oxide nanoparticles with a maghemite structure, mannitol, inulin, and Arabic gum. In previous analytical tests, C-PAM had a superior Pi-binding capacity compared to major approved Pi-binders. The hypothesis of this experimental in vivo study is that C-PAM more efficiently lowers serum Pi compared to those Pi-binders.

Methods

Healthy male Sprague-Dawley rats with a starting weight of 250 g were treated with drug co-feeding for 4 weeks (n=8 rats per group). C-PAM was added to Altromin standard 1320 diet (containing 0.6 wt% free adsorbable Pi) at 0.125, 0.25, and 0.5 wt% Fe. For comparison, three groups received Fosrenol® at 0.25 wt% La, Renvela® at 0.5 wt% sevelamer carbonate, and Velphoro® at 0.25 wt% Fe. As controls, one group received standard diet only and one group the carbohydrate components of C-PAM (mannitol, inulin, Arabic gum) at 2.0 wt%. Blood was sampled at the end of the 4-week study period and analyzed for serum Pi and standard parameters of hematology and clinical chemistry. For histopathology, HE and iron stains of liver, spleen, heart, lung, kidney, stomach, duodenum, jejunum, ileum, colon, and intestinal lymph nodes were assessed. Student's t-test was used for statistical analysis.

Results

At all doses investigated, C-PAM reduced serum Pi significantly (0.125 wt%: p <.05, 0.25 and 0.5 wt%: p <.01). None of the other products tested or the carbohydrate components of C-PAM had a significant serum Pi lowering effect (figure). For C-PAM, except serum Pi, there was no effect on hematology and clinical chemistry parameters. No histopathologic changes were observed.

Conclusion

Even at a low dose, C-PAM effectively reduces serum Pi in healthy rats and thus is superior to three major approved products.

In vivo efficacy of C-PAM in lowering serum Pi at three different doses compared with three approved products, the carbohydrate components of C-PAM only, and with a control group (*p<.05; **p<.01).

Funding

  • Government Support - Non-U.S.