Presystemic and systemic intestinal metabolism of fenoterol in the conscious rat
Koster, A.S.; Hofman, G.A.; Frankhuijzen-Sierevogel, A.C.; Noordhoek, J.
Drug Metabolism and Disposition the Biological Fate of Chemicals 13(4): 464-470
1985
ISSN/ISBN: 0090-9556 PMID: 2863112 Document Number: 248682
The intestinal and liver first pass metabolism of fenoterol hydrobromide value after intraduodenal, intraportal and i.v. administration. Saturation of intestinal and/or liver metabolism was checked by using 3 dose levela t 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 i.v. infusion (30 .mu.g fenoterol/min per kg), an intestinal extraction ratio of EG = 0.26 was observed. After i.v. administration of fenoterol (1 and 2 mg/kg), dose-dependent pharmacokinetics were observed. Doubling of the dose resulted in an increase of systemic clearance (CI = 53.8 .+-. 2.7 and 74.4 .+-. 1.8 ml/min per kg) and distribution volume (Vss = 0.95 .+-. 0.13 and 1.21 .+-. 0.11 l/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.