Open AccessInfluence of omeprazole on pharmacokinetics of domperidone given as free base and maleate salt in healthy Chinese patients
Author(s) -
ZHANG Yifan,
CHEN Xiaoyan,
DAI Xiaojian,
ZHANG Yini,
LIU Qizhi,
YU Hualing,
ZHONG Dafang
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00596.x
Subject(s) - domperidone , omeprazole , pharmacokinetics , crossover study , chemistry , free base , pharmacology , washout , salt (chemistry) , medicine , placebo , dopamine , alternative medicine , pathology
Aim: To investigate the influence of omeprazole on the pharmacokinetics of domperidone given as free base and maleate salt. Methods: An open, randomized, 2‐period crossover study with a washout period of 7 d was conducted in 10 healthy Chinese, male patients. In each study period, the patients were administered a single oral dose of 10 mg domperidone as free base or maleate salt on d 1, 20 mg omeprazole twice daily on d 2 and 3, and once on d 4. A single dose of 10 mg domperidone as free base or maleate salt was taken at 4 h after administration of omeprazole on d 4. Plasma samples were collected on d 1 and 4 after the administration of domperidone, and the plasma concentrations of domperidone were determined by a sensitive liquid chromatography‐tandem mass spectrometry method. Results: For free‐base domperidone, pretreatment with omeprazole resulted in a 16% decrease in maximum concentration (C max ), compared with administration alone ( P < 0.05). However, for maleate salt, with the exception of an increase in t 1/2 , no pharmacokinetic parameters were significantly changed. When the free base and maleate salt were administered alone, no differences were found in any parameters between the 2 formulations. In contrast, when they were administered in the presence of omeprazole, the C max of domperidone given as free base was lower (25.9%) than that given as maleate salt ( P < 0.05). Conclusion: Pretreatment of omeprazole does not affect the absorption of domperidone maleate, but leads to a moderately decreased rate of absorption of the free base.