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Pharmacokinetics of oral amlodipine orotate in vagotomized dogs
Author(s) -
Kwak Hyun H.,
Kim Jong O.,
Chung Han K.,
Choi Seul M.,
Kim Jung H.,
Kwon Jong W.,
Yoo Moohi,
Lee Joo H.,
Lee Myung G.
Publication year - 2006
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.495
Subject(s) - pharmacokinetics , amlodipine , pharmacology , medicine , blood pressure
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.