Influence of omeprazole on pharmacokinetics of domperidone given as free base and maleate salt in healthy Chinese patients
Abstract
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 t½, 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.
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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 t½, 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.