Effects of Glipizide on the Pharmacokinetics of Carvedilol after Oral and Intravenous Administration in Rats

scavenges free radicals of oxygen (Feuerstein et al., 1997). It is used to treat systemic arterial hypertension (Cournot et al., 1992; Lund-Johansen et al., 1992) and congestive heart failure (DasGupta et al., 1991) and is purported to improve exercise capacity (Cleland et al., 1996; Hampton, 1996) and longevity in humans (Bristow et al., 1996). Carvedilol is well absorbed from the gastrointestinal tract, but is subject to considerable fi rst-pass metabolism in the intestinal and/or liver (McTavish et al., 1993; Morgan, 1994). Carvedilol is more than 98% bound to plasma proteins. Carvedilol is metabolized by both oxidation and conjugation pathways in the liver into some metabolites (Neugebauer et al., 1987; Neugebauer and Neubert, 1991). The oxidation pathways are mainly catalyzed by CYP2C9 enzymes in human (McTavish et al., 1993; Morgan, 1994; Oldham and Clarke, 1997), and then CYP2D6 is responsible for the formation of 4’-hydroxy carvedilol and 5’-hydroxy carvedilol, and both metabolites are excreted into urine (Neugebauer and Neubert, 1991). Since carvedilol is a substrate of both CYP2C9 enOriginal Article Biomol Ther 19(2), 237-242 (2011)