An 1H NMR study of the cytarabine degradation in clinical conditions to avoid drug waste, decrease therapy costs and improve patient compliance in acute leukemia

Claudio Cerchione, Giovanni Martinelli, Silvana Pedatella, Mauro De Nisco, Novella Pugliese, Michele Manfra, Nicoletta Marra, Sonia Ronconi, Ugo De Giorgi, Mattia Altini, Giorgia Simonetti, Andrea Ghelli Luserna Di Rorà, Sara Bravaccini, Lucio Catalano, Vita Dora Iula, Francesco Pagano, Marco Picardi, Adele Bolognese, Fabrizio Pane, Vincenzo Martinelli

Research output: Contribution to journalArticle

Abstract

Cytarabine, the 4-amino-1-(β-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C) is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers' instructions, once the components-sterile water and cytarabine powder-are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4°C. To evaluate how to avoid wasting the drug in short-term, low-dose treatment regimens, the reconstituted samples, stored at 25°C and 4°C, were analyzed every day of the test week by reversed-phase HPLC and high-field NMR spectroscopy. All the samples remained unchanged for the entire week, which corresponds to the time required to administer the entire commercial drug package during low-dose therapeutic regimens. The drug solution was stored in a glass container at 4°C in an ordinary freezer and drawn with sterile plastic syringes; during this period, no bacterial or fungal contamination was observed. Our findings show that an cytarabine solution prepared and stored in the original vials retains its efficacy and safety and can, therefore, be divided into small doses to be administered over more days, thus avoiding unnecessary expensive and harmful waste of the drug preparation. Moreover, patients who require daily administration of the drug could undergo the infusion at home without need to go to hospital. The stability of the aliquots would help decrease hospitalization costs.

Original languageEnglish
Pages (from-to)67-72
Number of pages6
JournalAnti-Cancer Drugs
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 1 2020

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

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