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Pharmacokinetics of ethopropazine in the rat after oral and intravenous administration
Author(s) -
MaboudianEsfahani Mojdeh,
Brocks Dion R.
Publication year - 1999
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199904)20:3<159::aid-bdd164>3.0.co;2-d
Subject(s) - pharmacokinetics , bioavailability , oral administration , cmax , pharmacology , urine , chemistry , medicine , endocrinology
The pharmacokinetics of the anticholinergic drug ethopropazine (ET) have been 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 13 096±4186 ng h/mL ( n =5 rats), respectively. The t 1/2 after 5 and 10 mg/kg iv doses were 17.9±3.3 and 20.9±6.0 h, respectively. The Cl 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 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 t 1/2 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 iv doses. The drug displayed poor bioavailability (<5%) after oral administration. Copyright © 1999 John Wiley & Sons, Ltd.