Phenazone as a marker of liver-metabolic function in patients with acute leukemia.
OBJECTIVE
The aim of this work was to study the influence of neoplastic disease, especially acute myeloblastic leukemia (AML), and its chemotherapy on the activity of hepatic microsomal enzymes by using phenazone, as a marker of oxidative drug metabolizing activity.


METHODS
The observations were carried out in 21 patients with AML and in 53 healthy volunteers. The influence of disease on phenazone kinetics was studied before chemotherapy and the effect of anticancer drugs administration after the first cycle of chemotherapy.


RESULTS
The mean phenazone half-life time was significantly shorter in patients with AML (8.79 (3.01) h) than in control group (11.08 (3.61) h) (p < 0.012). Treatment with anticancer drugs, especially with epirubicine, inhibited phenazone elimination. The mean phenazone half-life time was significantly longer (18.08 (8.80) h) and the mean metabolic clearance rate was significantly smaller (33.92 (15.40) ml/min) after chemotherapy in comparison with the initial value, before treatment (10.22 (2.90) h), (p < 0.01) (50.33 (20.29) ml/min) (p < 0.008).


CONCLUSIONS
Our results lead to the conclusion that phenazone is an important index of hepatic metabolic capacity in patients with acute myeloblastic leukemia. The evaluation of its kinetics allowed to early recognition of the presence and the degree of drug oxidizing modification. Acceleration of phenazone elimination before treatment and its inhibition after chemotherapy, particulary epirubicine, may suggest that in patients with AML elimination of the other drugs metabolized by the pathway similar to phenazone also may be changed. It should be considered in individualization of their dosage regimen.
Wiela-Hojenska
A
A
Department of Clinical Pharmacology, Wroclaw University of Medicine, Poland.
Orzechowska-Juzwenko
K
K
Usnarska-Zubkiewicz
L
L
Kotlarek-Haus
S
S
Hurkacz
M
M
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D000983:Antipyrine / Q000097:blood / Q000493:pharmacokinetics*; D015415:Biomarkers; D001711:Biotransformation / Q000187:drug effects; D015251:Epirubicin / Q000494:pharmacology; D005260:Female; D006207:Half-Life; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D015415:Biomarkers; D015251:Epirubicin; D000983:Antipyrine