Metabolite Profiles of Flutamide in Serum from Patients with Flutamide-Induced Hepatic Dysfunction

Hepatic dysfunction due to flutamide administration has been reported and this side effect often limits the use of the agent. The prediction of flutamide-induced hepatotoxicity is attributed to the proper use of the antiandrogen. In this study, we investigated whether hepatic dysfunction could be as...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2003, Vol.26(10), pp.1455-1460
Main Authors: Takashima, Eiji, Iguchi, Kazuhiro, Usui, Shigeyuki, Yamamoto, Hajime, Hirano, Kazuyuki
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Antineoplastic agents
Biological and medical sciences
Chemical and Drug Induced Liver Injury
flutamide
Flutamide - adverse effects
Flutamide - blood
Flutamide - chemistry
General aspects
hepatotoxicity
Humans
Liver Diseases - blood
Medical sciences
metabolite profile
Middle Aged
Pharmacology. Drug treatments
risk prediction
serum
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Summary:Hepatic dysfunction due to flutamide administration has been reported and this side effect often limits the use of the agent. The prediction of flutamide-induced hepatotoxicity is attributed to the proper use of the antiandrogen. In this study, we investigated whether hepatic dysfunction could be assessed by the metabolite profile in serum from patients receiving this drug. Serum samples were obtained from 15 patients with prostate cancer, 12 patients with no sign of hepatotoxicity and 3 patients with slight hepatic dysfunction during long-term flutamide treatment. We analyzed the metabolite profiles by LC/MS in selected ion monitoring mode and detected a new metabolite (M3) that was an oxidation product of flutamide. However, there were no consistent differences in the serum flutamide metabolites between patients with normal function and those suffering hepatic dysfunction. The metabolite profiles in the β-glucuronidase-treated serum showed a similar pattern between normal functioning and dysfunctional groups. Thus, the profile of flutamide metabolites determined in serum may not contribute to the risk prediction of flutamide-related hepatotoxicity.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.26.1455