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Pharmacokinetics of oral amlodipine orotate in vagotomized dogs

✍ Scribed by Hyun H. Kwak; Jong O. Kim; Han K. Chung; Seul M. Choi; Jung H. Kim; Jong W. Kwon; Moohi Yoo; Joo H. Lee; Myung G. Lee

Publisher: John Wiley and Sons
Year: 2006
Tongue: English
Weight: 77 KB
Volume: 27
Category: Article
ISSN: 0142-2782
DOI: 10.1002/bdd.495

No coin nor oath required. For personal study only.

✦ Synopsis

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.

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