Influence of omeprazole on pharmacokinetics of domperidone given as free base and maleate salt in healthy Chinese patients.
OBJECTIVE
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).


CONCLUSIONS
Pretreatment of omeprazole does not affect the absorption of domperidone maleate, but leads to a moderately decreased rate of absorption of the free base.
Zhang
Yi-fan
YF
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Chen
Xiao-yan
XY
Dai
Xiao-jian
XJ
Zhang
Yi-ni
YN
Liu
Qi-zhi
QZ
Yu
Hua-ling
HL
Zhong
Da-fang
DF
D000328:Adult; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004294:Domperidone / Q000493:pharmacokinetics*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D018492:Dopamine Antagonists; D004294:Domperidone; D009853:Omeprazole