Flutamide投与前立腺癌患者における血清中代謝物濃度と肝機能異常の検討
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1)Flutamide投与11週目に重篤な肝障害を発現した症例の血清中代謝物濃度を測定したところ,flutamide濃度が通常よりも高く,OH-flutamideへの代謝が低下していた.2)37名の前立腺癌患者の血清中代謝物濃度を測定し,GOT及びGPTとの関係を調べたところ,肝機能異常例では肝機能の正常な例に比べ,flutamide濃度が高かった.3)Flutamide投与による軽度から中等度の肝機能異常例では,投薬中止により,GOT及びGPTは正常値に回復した.4)肝機能異常は32週迄に発現し,それ以上の長期投与可能症例では,肝機能異常は起らず,flutamide投与期間及び総投与量に依存しなかった.5)Flutamideによる重篤な肝障害を防ぐために,患者への問診や服薬指導を行いながら,定期的な肝機能検査を行い,GOT及びGPT等のマーカーが上昇した場合には速やかに投与を中止することが必要であるSevere hepatotoxicity occurred in a prostate cancer patient treated with 375 mg of flutamide per day, 125 mg three times a day, for 11 weeks. Serial measurements of serum concentrations of flutamide and its metabolites in the patient showed an unusually high serum level and delayed elimination of flutamide and suggested decreased metabolic activity of oxidation of flutamide to OH-flutamide. In 37 patients with prostate cancer we periodically monitored the serum concentrations of flutamide as well as liver function parameters. In 2 patients, glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) elevated over 100 IU/L, and treatment with flutamide was discontinued. Slight elevation of GOT and GPT over 40 to 100 IU/L was also detected in 5 patients, and flutamide was withdrawn. The elevated GOT and GPT in these 7 patients recovered to the pretreatment levels after discontinuation of the treatment. In these patients with flutamide-induced hepatic disorders, the average serum concentration of flutamide was higher (2.76 times, and that of OH-flutamide was lower (0.76 times), as compared with patients who maintained normal liver function.