Pharmacokinetic studies on Elobromol in children with brain tumors

C. Paal, V. Erdelyi-Toth, E. Pap, C. Csaki, T. Ferencz, D. Schuler, J. D. Borsi

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Systemic pharmacokinetics of high dose (500 mg/m2), orally administered Elobromol (dibromodulcitol, DBD) were studied in 16 chemotherapeutic courses administered to five patients. Cerebrospinal fluid (CSF) DBD levels were also analyzed in two patients. Bromoepoxydulcitol (BED), dianhydrodulcitol (DAD) are cytotoxic, whereas bromoanhydrodulcitol (BAD) and anhydroepoxydulcitol (AED) are inactive metabolites detectable during the biotransformation of DBD. The HPLC method, developed by our team, is suitable for the determination of both DBD and its main metabolites (DAD and BAD). Our publication is the first in the literature to describe the pharmacokinetic properties of these three hexitol derivatives in pediatric patients. With the exception of one patient, concentration time curves were analyzed by the one-compartment model. From 30 min following administration, DBD was detectable in all plasma samples for at least 12 h; its concentration, however, was usually undetectable by 24 h. Though highly variable in value, DAD concentrations were detectable during all but one of the therapeutic courses. The following peak concentrations were observed: DBD = 3.46-30.63 μM, DAD = 1.70-6.17 μM and BAD = 0-5.63 μM. The correlation of AUC(BAD) and AUC(DBD) values were exponential up to 200 μM h with no additional increase detectable above this limit: the distribution of AUC(BAD) and AUC(DBD) was described by a maximum curve. The possibility of enterohepatic recirculation could not be excluded for any of the compounds studied. Each of the three hexitol derivatives was detectable in CSF even if the concentration of the individual metabolite remained undetectable in plasma. DBD CSF concentrations were almost constant in the period from 2.5 to 8 h following administration. Due to rising DAD concentrations, however, the value of the CSF/plasma concentration ratio was >1. The cumulation of the inactive BAD metabolite in CSF was also significant.

Original languageEnglish
Pages (from-to)539-547
Number of pages9
JournalAnti-Cancer Drugs
Issue number5
Publication statusPublished - Oct 21 1994



  • brain tumor
  • children
  • dibromodulcitol
  • pharmacokinetics

ASJC Scopus subject areas

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

Cite this

Paal, C., Erdelyi-Toth, V., Pap, E., Csaki, C., Ferencz, T., Schuler, D., & Borsi, J. D. (1994). Pharmacokinetic studies on Elobromol in children with brain tumors. Anti-Cancer Drugs, 5(5), 539-547.