Pharmacokinetics of ethopropazine in the rat after oral and intravenous administration

The pharmacokinetics of the anticholinergic drug ethopropazine (ET) have be en studied in the rat after intravenous (iv) and oral administration. After iv 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. Th e t(1/2) after 5 and 10 mg/kg iv doses were 17.9 +/- 3.3 and 20.9 +/- 6.0 h , respectively. The CI and V-dss after 5 mg/kg iv doses were 0.48 +/- 0.10 L/h/kg and 7.1 +/- 2.3 L/kg, respectively. Statistically significant differ ences 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 268 5 +/- 336 ng h/mL. Mean plasma C-max,t(max) and t(1/2) after oral doses wer e 236 +/- 99 ng/mL, 2.2 +/- 1.4 h and 26.1 +/- 5.4 h, respectively. Less th an 1% of the dose was recovered unchanged in urine and bile. Ethopropazine is extensively distributed in the rat, and has relatively slow Cl in relati on to hepatic blood flow in the rat. The drug appears to be extensively met abolized in the rat, and nonlinearity is present between the 5 and the 10 m g/kg iv doses. The drug displayed poor bioavailability ( < 5%) after oral a dministration. Copyright (C) 1999 John Wiley & Sons, Ltd.