Koster A S, Hofman G A, Frankhuijzen-Sierevogel A C, Noordhoek J
Drug Metab Dispos. 1985 Jul-Aug;13(4):464-70.
The intestinal and liver first pass metabolism of fenoterol.HBr (Berotec, Partusisten) was investigated in the conscious rat. Fenoterol plasma concentrations (2-1000 ng/ml) were measured with a new HPLC determination using electrochemical detection. After intraduodenal administration, fenoterol was incompletely absorbed (47-66% not absorbed). Presystemic intestinal (EGpre) and liver (EH) extraction ratios, EGpre = 0.93 +/- 0.01, EH = 0.67 +/- 0.04, were calculated from AUC values after intraduodenal, intraportal, and iv administration. Saturation of intestinal and/or liver metabolism was checked by using three dose levels at different administration routes. Total systemic availability after intraduodenal administration ranged from 0.8 (10 mg/kg) to 1.2% (40 mg/kg). The contribution of the splanchnic region to the systemic clearance of fenoterol was assessed by measuring fenoterol and fenoterol-glucuronide concentrations in arterial and portal venous blood under steady state conditions. During iv infusion (30 micrograms fenoterol/min X kg), an intestinal extraction ratio of EG = 0.26 was observed. After iv administration of fenoterol (1 and 2 mg/kg), dose-dependent pharmacokinetics were observed. Doubling of the dose resulted in an increase of systemic clearance (Cl = 53.8 +/- 2.7 and 74.4 +/- 1.8 ml/min X kg) and distribution volume (Vss = 0.95 +/- 0.13 and 1.21 +/- 0.11 liters/kg); the mean residence time (17.9 +/- 2.4 and 16.3 +/- 1.4 min) and terminal half-life (45.8 +/- 5.5 and 46.8 +/- 2.8 min) were not changed.
对氢溴酸非诺特罗（备劳特，Partusisten）在清醒大鼠体内的肠道及肝脏首过代谢进行了研究。采用一种新的高效液相色谱电化学检测法测定非诺特罗的血浆浓度（2 - 1000纳克/毫升）。十二指肠内给药后，非诺特罗吸收不完全（47 - 66%未被吸收）。根据十二指肠内、门静脉内及静脉注射给药后的曲线下面积值计算出肠内（EGpre）和肝脏（EH）的首过提取率，EGpre = 0.93±0.01，EH = 0.67±0.04。通过在不同给药途径下使用三个剂量水平来检查肠道和/或肝脏代谢的饱和情况。十二指肠内给药后的总全身生物利用度范围为0.8%（10毫克/千克）至1.2%（40毫克/千克）。通过在稳态条件下测量动脉血和门静脉血中非诺特罗及非诺特罗 - 葡萄糖醛酸苷的浓度，评估了内脏区域对非诺特罗全身清除率的贡献。静脉输注期间（30微克非诺特罗/分钟×千克），观察到肠内提取率EG = 0.26。静脉注射非诺特罗（1和2毫克/千克）后，观察到剂量依赖性药代动力学。剂量加倍导致全身清除率（Cl = 53.8±2.7和74.4±1.8毫升/分钟×千克）和分布容积（Vss = 0.95±0.13和1.21±0.11升/千克）增加；平均驻留时间（17.9±2.4和16.3±1.4分钟）和末端半衰期（45.8±5.5和46.8±2.8分钟）未改变。
