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 (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.
Kwak
Hyun H
HH
Research Laboratory, Dong-A Pharmaceutical Company Ltd, Yongin, Republic of Korea.
Kim
Jong O
JO
Chung
Han K
HK
Choi
Seul M
SM
Kim
Jung H
JH
Kwon
Jong W
JW
Yoo
Moohi
M
Lee
Joo H
JH
Lee
Myung G
MG
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
D002121:Calcium Channel Blockers; D013607:Tablets; D017311:Amlodipine