抗アンドロゲン剤TZP-4238の臨床薬理試験 : 腎機能に関する検討

Abstract

TZP-4238の腎機能に関し検討した。1)単回投与試験:1)前立腺肥大症患者をそのCCrにより, A群(CCr<50ml/min), B群(CCr≧50ml/min)に分けTZP-4238単回投与時の血中動態を比較検討した。2) TZP-4238はA群とB群で同様の血中動態を示し, 各薬物動態パラメーターおよび血清蛋白結合率に有意な差はなかった。15-OH体についても両群で同様の血中動態を示した。3) TZP-4238, 15-OH体の尿中排泄率はともに両群間に有意な差はなかった。2)連続投与試験:1)比較的腎機能の低下した前立腺肥大症患者を対象に16週間の連続投与試験を実施した。2)血清中濃度を測定した5例についてはA群の結果から描いたシミュレーションと良く一致した。3)有効率は71.4%, 安全率は90.0%, 有用率は71.4%であった

The effect of TZP-4238, an antiandrogen drug, on renal function was examined. Single administration test: Patients with prostatic hypertrophy were divided according to creatinine clearance (CCr) into group A (CCr or = 50 ml/min), and hemodynamics after a single administration of TZP-4238 were compared between the two groups. Groups A and B showed similar TZP-4238 hemodynamics, and there was no significant difference in pharmacokinetic parameters or the rate of serum protein binding between them. There was no difference in the hemodynamics of a major metabolite, 15-OH body, between the two groups. Neither was there any significant difference in the urinary excretion rate of TZP-4238 or 15-OH body. There were no findings of adverse clinical significance, and there were no problems with safety. Consecutive administration test: A 16-week consecutive administration study was performed on patients with prostatic hypertrophy associated with relative renal hypofunction. The blood levels determined in 5 patients were in good accordance with the simulation curve drawn from the results of group A. The rates of efficacy, safety and usefulness were 71.4%, 90% and 71.4%, respectively. Mild side effects were observed in one patient, but the 16-week administration was completed in all patients, and no adverse effects on renal function were observed. Favorable blood levels of TZP-4238 were obtained even in patients with prostatic hypertrophy associated with renal hypofunction, and adequate efficacy and safety were achieved even with consecutive administration. Furthermore, the drug had no apparent adverse effect on renal function.