title: Pharmacokinetics of oral amlodipine orotate in vagotomized dogs.
abstract: 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 (Tmax) 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 Tmax was significantly shorter (1.50 versus 5.00 h) than those in dogs without vagotomy.
authors.affiliation: Research Laboratory, Dong-A Pharmaceutical Company Ltd, Yongin, Republic of Korea.
authors.forename: Hyun H
authors.initials: HH
authors.lastname: Kwak
authors.forename: Jong O
authors.initials: JO
authors.lastname: Kim
authors.forename: Han K
authors.initials: HK
authors.lastname: Chung
authors.forename: Seul M
authors.initials: SM
authors.lastname: Choi
authors.forename: Jung H
authors.initials: JH
authors.lastname: Kim
authors.forename: Jong W
authors.initials: JW
authors.lastname: Kwon
authors.forename: Moohi
authors.initials: M
authors.lastname: Yoo
authors.forename: Joo H
authors.initials: JH
authors.lastname: Lee
authors.forename: Myung G
authors.initials: MG
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D017311:Amlodipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004285:Dogs; D005769:Gastrointestinal Motility / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008657:Metabolic Clearance Rate; D023421:Models, Animal; D012995:Solubility; D013607:Tablets; D013997:Time Factors; D014628:Vagotomy
chemical_list: D002121:Calcium Channel Blockers; D013607:Tablets; D017311:Amlodipine