title: Presystemic and systemic intestinal metabolism of fenoterol in the conscious rat.
abstract: 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.
authors.forename: A S
authors.initials: AS
authors.lastname: Koster
authors.forename: G A
authors.initials: GA
authors.lastname: Hofman
authors.forename: A C
authors.initials: AC
authors.lastname: Frankhuijzen-Sierevogel
authors.forename: J
authors.initials: J
authors.lastname: Noordhoek
mesh_terms: D000818:Animals; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004386:Duodenum; D004983:Ethanolamines / Q000378:metabolism*; D005280:Fenoterol / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D007263:Infusions, Parenteral; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D011169:Portal Vein; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D004983:Ethanolamines; C046350:fenoterol glucuronide; D005280:Fenoterol