Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Phenazone pharmacokinetics as a marker of drugs biotransformation in children with acute lymphoblastic leukemia during chemotherapy

A Wiela-Hojenska PharmD 1, K Orzechowska-Juzwenko MD PhD 1, E Gorczynska PhD 2, W Golebiowski PhD 2, J Boguslawska-Jaworska MD PhD 2

1 Dept Clinical Pharmacology,, 2 Dept and Clinic of Pediatric Haematology, Wroclaw Medical University, Wroclaw, Poland

AIM: The purpose of our work was estimation of liver function, by phenazone test, in children with acute lymphoblastic leukemia (ALL) during anticancer treatment. METHODS: Observations were carried out in 21 patients with ALL before the beginning of chemotherapy, after protocol I and after protocol M of the antileukemic treatment according to programme BFM 86. RESULTS: Applied chemotherapy inhibited phenazone elimination. In-patients with ALL after anticancer treatment, especially with high-dose of methotrexate, the mean phenazone half-life time was significantly (p<0,001) longer and metabolic clearance rate was significantly (p<0,001) reduced that in patients before the beginning of chemotherapy. CONCLUSION: Our results showed that in children with acute lymphoblastic leukemia anticancer chemotherapy decreased liver metabolic capacity. Particularly, high-dose methotrexate treatment altered the elimination of phenazone by inhibiting the activity of hepatic mixed function oxidase system. It may lead to increase of toxicity of all drugs, which are metabolized by this enzyme system and should be considered in selection of individual dosage.

KEY WORDS: children , acute lymphoblastic leukemia , anticancer treatment, liver metabolic function, phenazone test.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on chemotherapy.