Fuse E, Takai K, Kobayashi H, Kobayashi S
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.
Gan To Kagaku Ryoho. 1997 Jun;24(8):975-9.
The hepatic extraction ratios (EH) of adriamycin (ADR) and mitomycin C (MMC), which were administered clinically by an intra-hepatic arterial route, were measured in rats to clarify the disposition of ADR and MMC in liver. EH values of ADR and MMC were determined by comparing the femoral arterial and hepatic venous plasma concentrations at steady state during continuous intravenous administration. The EH value of ADR in rats at each infusion rate of 2, 10 and 50 micrograms/kg/min, was 0.290, 0.286 and 0.251, respectively. There was no significant difference between the EH values (p > 0.05). The systemic clearance (CLtot) at each infusion rate was 108, 77.6 and 72.9 ml/min/kg, respectively. The EH value of MMC in rats at each infusion rate of 2.5, 7.5 and 25 micrograms/kg/min, was 0.332, 0.358 and 0.360, respectively. There was no significant difference between the EH values, the same as for ADR. The systemic clearance (CLtot) at each infusion rate was 38.3, 36.1 and 35.3 ml/min/kg.
为明确阿霉素(ADR)和丝裂霉素C(MMC)在肝脏中的处置情况,对经肝动脉途径临床给药的大鼠测定了这两种药物的肝提取率(EH)。通过比较持续静脉给药稳态时股动脉和肝静脉血浆浓度来确定ADR和MMC的EH值。ADR在大鼠中以2、10和50微克/千克/分钟的各输注速率下的EH值分别为0.290、0.286和0.251。EH值之间无显著差异(p>0.05)。各输注速率下的全身清除率(CLtot)分别为108、77.6和72.9毫升/分钟/千克。MMC在大鼠中以2.5、7.5和25微克/千克/分钟的各输注速率下的EH值分别为0.332、0.358和0.360。与ADR一样,EH值之间无显著差异。各输注速率下的全身清除率(CLtot)分别为38.3、36.1和35.3毫升/分钟/千克。