Influence of food on the gastric motor effect of the Kampo medicine rikkunshito in rat.

Abstract

Rikkunshito, one of the Kampo medicines, is widely prescribed as a remedy for various upper gastrointestinal syndromes. The effect of rikkunshito is related to endogenous ghrelin and its active ingredient atractylodin enhances ghrelin receptor signaling. Kampo medicines are traditionally administered before or between meals; however, no definitive benefit of the timing of administration has been proven yet. To clarify the influence of food on the pharmacological action of rikkunshito, we investigated the gastric motor activity and pharmacokinetic profiles of atractylodin after the administration of rikkunshito in fasted and fed rats. Phase III-like contractions in the gastric antrum after an injection of ghrelin were measured using a strain gauge force transducer. Rikkunshito was administered to rats during fasting or after a nutrient test meal. Ghrelin was injected 30minutes later and gastric motility was evaluated. Furthermore, after rikkunshito administration, the pharmacokinetic profiles of atractylodin in the plasma and brain of fasted and free-fed rats were assessed. Rikkunshito administration potentiated ghrelin-induced phase III-like contractions under fasting conditions. This effect was attenuated in animals fed a test meal. Atractylodin was detected pharmacokinetically in the plasma and brain after rikkunshito administration in rats, and free-fed rats exhibited a decreased maximum concentration of plasma atractylodin and a delayed time to reach the maximum concentration. We show that the pharmacological action of rikkunshito is influenced by food in rats. The efficacy of rikkunshito may be associated with decreased absorption of its active ingredient atractylodin when food is in the stomach.