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

Abstract

Abstractscavenges 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 .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 en-

The Pharmacokinetic Interaction Study between Carvedilol and Bupropion in Rats

“…These results were consistent with the results of previous reports indicating other CYP450 inhibitors, including ketoconazole [20], cilostazol [21], glipizide [22], and ticlopidine [23], which increased the plasma levels of carvedilol in rats to a similar extent as that of bupropion.…”

Inhibitory Effect of Citalopram on the Pharmacokinetics of Carvedilol in Rats and in vitro Models

“…Other PK drug-drug interaction studies between carvedilol and CYP450 inhibitors, including ketoconazole [30], cilostazol [31], ticlopidine [32], glipizide [33,] and bupropion [34] showed an increase in the carvedilol plasma levels in rats to a similar extent as that created by citalopram in the present study. Moreover, there are few clinical trials that evaluated carvedilol PKs after co-administration with fluoxetine [35] and paroxetine [36].…”