Pharmacokinetics of ethopropazine in the rat after oral and intravenous administration

✍ Scribed by Mojdeh Maboudian-Esfahani; Dion R. Brocks

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 115 KB
• Volume: 20
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199904)20:3<159::aid-bdd164>3.0.co;2-d

✦ Synopsis

The pharmacokinetics of the anticholinergic drug ethopropazine (ET) have been studied in the rat after intravenous (i.v.) and oral administration. After i.v. doses of 5 and 10 mg/kg ET HCl, mean +/- S.D. plasma AUC were 9836 +/- 2129 (n = 4 rats) and 13096 +/- 4186 ng h/mL (n = 5 rats), respectively. The t1/2 after 5 and 10 mg/kg i.v. doses were 17.9 +/- 3.3 and 20.9 +/- 6.0 h, respectively. The Cl and V(dss) after 5 mg/kg i.v. doses were 0.48 +/- 0.10 L/h/kg and 7.1 +/- 2.3 L/kg, respectively. Statistically significant differences were present between the 5 and 10 mg/kg dose levels in Cl and V(dss). Oral administration of 50 mg/kg ET HCl (n = 5 rats) yielded mean AUC of 2685 +/- 336 ng h/mL. Mean plasma C(max), t(max) and t1/2 after oral doses were 236 +/- 99 ng/mL, 2.2 +/- 1.4 h and 26.1 +/- 5.4 h, respectively. Less than 1% of the dose was recovered unchanged in urine and bile. Ethopropazine is extensively distributed in the rat, and has relatively slow Cl in relation to hepatic blood flow in the rat. The drug appears to be extensively metabolized in the rat, and nonlinearity is present between the 5 and the 10 mg/kg i.v. doses. The drug displayed poor bioavailability (< 5%) after oral administration.