A dibrómdulcit farmakokinetikai vizsgálata agytumoros gyermekekben.

Translated title of the contribution: Pharmacokinetic study of dibromodulcitol in children with brain tumors

K. Paál, V. Erdélyi-Tóth, E. Pap, C. Csáki, T. Ferencz, D. Schuler, J. Borsi

Research output: Contribution to journalArticle

Abstract

Systemic pharmacokinetics of high-dose (500 mg/m2), orally administered dibromodulcitol (Elobromol) were studied in 16 chemotherapeutic courses administered to 5 patients. Cerebrospinal fluid dibromodulcitol levels were also analysed in two patients. Bromoepoxydulcitol, dianhydrodulcitol are cytotoxic, whereas bromoanhydrodulcitol, andhydroepoxydulcitol are inactive metabolites detectable during the biotransformation of dibromodulcitol. The HPLC method, developed by our team, is suitable for the determination of both dibromodulcitol and its main metabolites (dianhydrodulcitol and bromoanhydrodulcitol). Our publication is the first in the literature to describe the pharmacokinetic properties of these three hexite-derivatives in pediatric patients. With the exception of one patient, concentration-time curves were analysed by the one-compartment model. From the 30th minute following administration, dibromodulcitol was detectable in all plasma samples for at least 12 hours, its concentration however was usually undetectable by the 24th hour. Though highly variable in value, dianhydrodulcitol concentrations were detectable during all but one therapeutic courses. The following peak concentrations were observed: dibromodulcitol: 3.46-30.63 microM; dianhydroldulcitol: 1.70-6.17 microM; bromoanhydrodulcitol: 0-5.63 microM. The correlation of area under the curve for bromoanhydrodulcitol and dibromodulcitol was exponential up to 200 microMxh with no additional increase detectable above this limit; the distribution of dianhydrodulcitol values were 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 were detectable in the cerebrospinal fluid even if the concentration of the individual metabolite remained undetectable in plasma. The cerebrospinal fluid concentrations of dibromodulcitol were almost constant in the period from 2.5 to 8 hours following administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Original languageHungarian
Pages (from-to)2527-2534
Number of pages8
JournalOrvosi Hetilap
Volume135
Issue number46
Publication statusPublished - Nov 13 1994

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Mitolactol
Brain Neoplasms
Dianhydrogalactitol
Pharmacokinetics
Cerebrospinal Fluid
Biotransformation
Area Under Curve
High Pressure Liquid Chromatography
Pediatrics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Paál, K., Erdélyi-Tóth, V., Pap, E., Csáki, C., Ferencz, T., Schuler, D., & Borsi, J. (1994). A dibrómdulcit farmakokinetikai vizsgálata agytumoros gyermekekben. Orvosi Hetilap, 135(46), 2527-2534.

A dibrómdulcit farmakokinetikai vizsgálata agytumoros gyermekekben. / Paál, K.; Erdélyi-Tóth, V.; Pap, E.; Csáki, C.; Ferencz, T.; Schuler, D.; Borsi, J.

In: Orvosi Hetilap, Vol. 135, No. 46, 13.11.1994, p. 2527-2534.

Research output: Contribution to journalArticle

Paál, K, Erdélyi-Tóth, V, Pap, E, Csáki, C, Ferencz, T, Schuler, D & Borsi, J 1994, 'A dibrómdulcit farmakokinetikai vizsgálata agytumoros gyermekekben.', Orvosi Hetilap, vol. 135, no. 46, pp. 2527-2534.
Paál K, Erdélyi-Tóth V, Pap E, Csáki C, Ferencz T, Schuler D et al. A dibrómdulcit farmakokinetikai vizsgálata agytumoros gyermekekben. Orvosi Hetilap. 1994 Nov 13;135(46):2527-2534.
Paál, K. ; Erdélyi-Tóth, V. ; Pap, E. ; Csáki, C. ; Ferencz, T. ; Schuler, D. ; Borsi, J. / A dibrómdulcit farmakokinetikai vizsgálata agytumoros gyermekekben. In: Orvosi Hetilap. 1994 ; Vol. 135, No. 46. pp. 2527-2534.
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AU - Pap, E.

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AU - Ferencz, T.

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N2 - Systemic pharmacokinetics of high-dose (500 mg/m2), orally administered dibromodulcitol (Elobromol) were studied in 16 chemotherapeutic courses administered to 5 patients. Cerebrospinal fluid dibromodulcitol levels were also analysed in two patients. Bromoepoxydulcitol, dianhydrodulcitol are cytotoxic, whereas bromoanhydrodulcitol, andhydroepoxydulcitol are inactive metabolites detectable during the biotransformation of dibromodulcitol. The HPLC method, developed by our team, is suitable for the determination of both dibromodulcitol and its main metabolites (dianhydrodulcitol and bromoanhydrodulcitol). Our publication is the first in the literature to describe the pharmacokinetic properties of these three hexite-derivatives in pediatric patients. With the exception of one patient, concentration-time curves were analysed by the one-compartment model. From the 30th minute following administration, dibromodulcitol was detectable in all plasma samples for at least 12 hours, its concentration however was usually undetectable by the 24th hour. Though highly variable in value, dianhydrodulcitol concentrations were detectable during all but one therapeutic courses. The following peak concentrations were observed: dibromodulcitol: 3.46-30.63 microM; dianhydroldulcitol: 1.70-6.17 microM; bromoanhydrodulcitol: 0-5.63 microM. The correlation of area under the curve for bromoanhydrodulcitol and dibromodulcitol was exponential up to 200 microMxh with no additional increase detectable above this limit; the distribution of dianhydrodulcitol values were 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 were detectable in the cerebrospinal fluid even if the concentration of the individual metabolite remained undetectable in plasma. The cerebrospinal fluid concentrations of dibromodulcitol were almost constant in the period from 2.5 to 8 hours following administration.(ABSTRACT TRUNCATED AT 250 WORDS)

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