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

• Published in: Biological & pharmaceutical bulletin Vol. 26; no. 10; pp. 1455 - 1460
• Main Authors: Takashima, Eiji, Iguchi, Kazuhiro, Usui, Shigeyuki, Yamamoto, Hajime, Hirano, Kazuyuki
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.10.2003; Maruzen; Japan Science and Technology Agency
• 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; Antineoplastic agent; Human; Biological fluid; Metabolite; Toxicity; Liver; metabolite profile; Antiandrogen; Antihormone; Flutamide; hepatotoxicity; risk prediction; Risk factor; Digestive diseases; Serum; Pharmacokinetics; Non steroid compound
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.26.1455

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.