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

作　　者：Yi-fan ZHANG Xiao-yan CHEN Xiao-jian DAI Yi-ni ZHANG Qi-zhi LIU Hua-ling YU Da-fang ZHONG 

机构地区：[1]Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China [2]Shenyang Pharmaceutical University, Shenyang 110016, China [3]Beijing Hanmi Pharm, Beijing 101312, China

出　　处：《Acta Pharmacologica Sinica》2007年第8期1243-1246,共4页中国药理学报（英文版）

摘　　要：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 （Cmax）, compared with administration alone （P〈0.05）. However, for maleate salt, with the exception of an increase in t1/2, 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 Cmax 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.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 （Cmax）, compared with administration alone （P〈0.05）. However, for maleate salt, with the exception of an increase in t1/2, 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 Cmax 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.

关 键 词：DOMPERIDONE OMEPRAZOLE maleate salt free base PHARMACOKINETICS 

分 类 号：R96[医药卫生—药理学]