Effects of domperidone on human plasma levels of motilin, somatostatin, gastrin, adrenocorticotropic hormone and cortisol

Abstract

Domperidone, an upper gastrointestinal function regulatory medicine, has recently been evaluated for its clinical usefulness in the treatment of stress and depression. We examined the effects of domperidone on the plasma levels of motilin-immunoreactive substance (IS), somatostatin-IS, gastrin-IS, adrenocorticotropic hormone (ACTH)-IS, and cortisol under stress conditions by repetitive blood sampling. After a single oral administration of domperidone (30 mg), the plasma domperidone level was highest (58.6±6.4 ng/ml) in the sample taken 40 min after administration, after which the plasma level fell. Peak plasma motilin-IS levels (23.1±1.4 pg/ml) were achieved 40 min after administration of domperidone (p<0.01 vs. placebo), and returned to baseline levels within a further 40 min. Plasma somatostatin-IS levels (13.0±1.2 pg/ml) increased 60 min after administration of domperidone (p<0.01 vs. placebo). Plasma gastrin-IS levels did not change significantly. These results suggest that the pharmacological effects of domperidone on gastrointestinal functions are closely related to changes in motilin-IS and somatostatin-IS levels. Domperidone significantly suppressed increases in plasma ACTH-IS and cortisol levels compared with the response to a placebo. These modulatory effects might be beneficial in stress-related diseases and suggest that this medicine has clinical pharmacological activity. © 2005 Pharmaceutical Society of Japan.