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    Erste präklinische in vivo Studie zur Wirksamkeit eines Maghemitbasierten Wirkstoffes zur Behandlung der Hyperphosphatämie (2016)

    Art
    Hochschulschrift
    Autor
    Gläser, Janna Luisa (WE 12)
    Quelle
    Berlin: Mensch und Buch Verlag, 2016 — XI, 86 Seiten
    ISBN: 978-3-86387-701-9
    Verweise
    URL (Volltext): http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000101661
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
    +49 30 838 62450

    Abstract / Zusammenfassung

    Hyperphosphatemia secondary to chronic kidney disease is a very serious condition, causing cardiovascular morbidity and mortality. Unfortunately, currently available drugs have limited therapeutic effects. Hence, there is an urgent need for more effective medications. The aim of this study was to investigate the efficacy and safety of a new maghemite-based phosphate adsorbent, known as C-PAM-11, which was developed by the Experimental Radiology Section of Charité - Universitätsmedizin Berlin. The investigation was conducted as a four-week feeding trial was carried out. Healthy Sprague Dawley rats were fed a standard rat diet supplemented with the phosphate adsorbent over a period of four weeks. Once a week, they were housed in individual metabolic cages for 24 hours to collect urine and feces and measure food uptake. At the end of the study, the rats were sacrificed and blood, bones and organs were collected. Untreated control animals as well as animals treated with the current gold standard, Renvela® (Sevelamer carbonate), served as reference. Efficacy parameters were changes in urinary phosphate excretion, serum phosphate concentration and bone structure. Safety was assessed by observation of animals’ general condition, blood tests, and histologic examination of organ sections. After four weeks of treatment, renal phosphate excretion was drastically decreased. In addition, the serum phosphate concentration was diminished to such an extent that the C-PAM-11 treated animals developed hypophosphatemia. In contrast, the reference drug Renvela® did not lower the serum phosphate concentration. HRpQCT analysis of the bones also revealed the high efficacy of C-PAM-11. The different parameters measured showed that the animals developed osteomalacia. In summary, the striking effects observed in our study demonstrate the high efficacy of CPAM-11 treatment. More studies will follow to prove the effectiveness in animals with renal insufficiency and to identify a clinically applicable dose. The present study also shows good safety features of the new phosphate absorbent. Long-term experiments will follow to rule out toxicity through iron accumulation.