Pharmacokinetics of oral amlodipine orotate in vagotomized dogs

It was reported that gastric motility was delayed and gastric acid secretion was reduced in vagotomized dogs which mimics a low gastric acidity in humans. A delay in gastric motility causes long residence of amlodipine in the stomach. More unionized fractions of amlodipine could exist in less acidic conditions of gastrointestinal fluids, since amlodipine is a weak basic drug with pKa of 8.7. Hence, gastrointestinal absorption of amlodipine is expected to be enhanced and the time to reach a peak plasma concentration of amlodipine ( T max ) is faster in vagotomized dogs. This was proven after oral administration of an amlodipine orotate tablet at a dose of 5 mg as amlodipine in vagotomized dogs. For example, in vagotomized dogs, the total area under the plasma concentration–time curve from time zero to the last measured time, 48 h, in plasma ( AUC 0–48 h ) was significantly greater (725 versus 348 ng h/ml) and T max was significantly shorter (1.50 versus 5.00 h) than those in dogs without vagotomy. Copyright © 2006 John Wiley & Sons, Ltd.