Effect of Metoclopramide and Propantheline Bromide on Plasma Carvedilol Concentrations in Rats

• Published in: Byōin yakugaku Vol. 25; no. 2; pp. 155 - 161
• Main Authors: HOKAMA, NOBUO, HOBARA, NORIO, KAMEYA, HIROMASA, OHSHIRO, SUSUMU, SAKANASHI, MATAO
• Format: Journal Article
• Language: English; Japanese
• Published: Japanese Society of Pharmaceutical Health Care and Sciences 1999
• Subjects: carvedilol; gastric emptying; metoclopramide; pharmacokinetic interaction; propantheline bromide
• ISSN: 0389-9098; 2185-9477
• DOI: 10.5649/jjphcs1975.25.155

We investigated the effects of metoclopramide and propantheline bromide on the bioavailability of carvedilol in rats. To determine the concentration-time profile of plasma carvedilol, the blood samples were obtained from the tail vein after the simultaneous administration of 20mg/ kg carvedilol either with or without 5 mg/kg metoclopramide and 15 mg/kg propantheline bromide. The plasma carvedilol concentrations were significantly higher than the controls at 15 min. -1 hr and 3, 4 hr, and the drug pharmacokinetic parameters time to Cmax (Tmax) was 0.45 time shorter, while the absorption rate constant (Ka) and area under the concentration-time curve (AUC0-24) were 2.5 and 1.5 times higher after the oral administration of carvedilol with metoclopramide. The rate of bioavailability for carvedilol was accelerated by metoclopramide which stimulates gastric emptying. In contrast, the plasma carvedilol concentrations and Tmax., A UC0-24 did not change after the single intraperitoneal administration of carvedilol with the oral administration of metoclopramide. Conversely, propantheline bromide, which delays gastric emptying, slowed absorption, but not according the AUC0-24 of carvedilol. Other similar pharmacokinetic interaction probably occur since carvedilol are poorly absorbed from the stomach and numerous therapeutic agents influence gastrointestinal motility.