The Prokinetic Effect of Mosapride Citrate on Horse Gastric Emptying Rates

Abstract

ABSTRACT. The prokinetic effect of the 5-HT 4 receptor agonist mosapride was evaluated in seven healthy thoroughbreds. Mosapride was orally administerd at doses of 0.5, 1.0 or 1.5 mg/kg. The breath 13 CO 2 / 12 CO 2 rate (∆ 13 CO 2 ), an indirect indicator for the rate of gastric empting, was measured at appropriate points for 4 hr after drug administration. There was a significant increase compared with the control value at 15, 20 and 165 min for 0.5 mg/kg, 30 min at 1.0 mg/kg and 165 min for 1.5 mg/kg. The results suggest that mosapride may facilitate the gastric emptying in horses. KEY WORDS: equine, gastric emptying rate, mosapride citrate.J. Vet. Med. Sci. 70(6): 627-628, 2008 Gastric emptying is delayed in horses with various gastrointestinal disorders including chronic or recurrent colic [2,[6][7][8] as well as postoperative ileus [1]. Delayed gastric emptying may not be only a consequence of these disorders but also may cause them. It actually dose cause anorexia and abdominal discomfort/pain, aggravating gastrointestinal disorders. A variety of prokinetic agents, including metoclopramide and cisapride, have been administered to horses in order to coordinate gastrointestinal motility [4,9], although they may produce unfavorable side effects on both the central nervous and cardiovascular systems [14]. Evidence has suggested that mosapride citrate (mosapride), a 5-HT 4 receptor-preferring agonist, is a more promising prokinetic [30,15]. This agent dose not interact with central dopamine receptors and hardly has any extrapyramidal side effects. It also has little activity in blocking cardiac K + channels and produces no significant ventricular arrhythmia with prolonged QT intervals [3,10]. However, the effect of mosapride on gastric emptying in horses has yet to be investigated.To do this, we used seven healthy thoroughbreds to examine the effect of orally-administrated mosapride on the rate of solid-phase gastric emptying using the 13 C-octanoate breath test.The animals used (1 mare and 6 geldings) had an average age of 5.6 ± 2.6 years (mean ± SD: n=7) and a mean body weight of 485.7 ± 46.9 kg (n=7). They were fed an ordinary diet (0.9 kg oats, 0.3 kg bran and 3.5 kg hay) twice daily and were allowed ad libitum access to water. The individual horses were each subjected to the breath test repeatedly at intervals of 7 to 9 days. Housing and care of the horses and the present study were in accordance with the protocol approved by the institutional animal care and use committee of Obihiro University.Breath samples were collected via a silicon tube inserted into the ventral nasal meatus, as described previously [12], and into zoo or 1,300 ml UBit ® -specialized breath sampling bags (Otsuka Pharmaceutical, Japan). The test meal consisted of 150 g oats, 100 g bran (200 mL in volume) and 500 mg 1 3 C-octanoate (1-13 C sodium octanoate, 99%; Wako Pure Chemical Industries, Japan) in 2 baked egg yolks. The test meal was ingested voluntarily.Mosapride (GASMOTIN ® Powder 1%) was purchased from Dainippon Sumitomo Pha...

Real-Time Ultrasonographic Evaluation of Canine Gastric Motility in the Postprandial State

“…Breath samples were collected before giving the test meal as a baseline, every 15 min after feeding for 4 hr, and every 30 min for additional 2 hr. The breath samples were analyzed using a 13 CO 2 -infrared spectrophotometry analyzer (POC one, Otsuka Pharmaceutical), which was previously used to assess gastric emptying in horses [20]. The amount of 13 C in the samples was expressed as the change ( 13 CO 2 , ‰) in the 13 CO 2 / 12 CO 2 ratio before and after feeding of the test meal.…”

The 5-HT4 receptor agonist prucalopride does not facilitate cholinergic neurotransmission in circular and longitudinal smooth muscle preparations of equine mid-jejunum

“…The selective 5-HT 4 receptor agonist mosapride dosedependently enhanced percutaneously measured electrical activity of equine cecum and small intestine, but the specific region of the small intestine was not mentioned (Sasaki et al, 2005). It also had a moderate facilitating effect on solid gastric emptying in horse but this effect was not dose-dependent (Okamura et al, 2008). Very recently, the influence of a single oral administration of prucalopride in horses with primary equine squamous gastric disease was reported; contractile frequency in the descending duodenum, cecum and left ascending colon was assessed by ultrasonography (Laus et al, 2017).…”

Pharmacokinetics of the Gastroprokinetic Agent Mosapride Citrate after Single Oral Administration in Horses

“…These results suggest that mosapride undergoes less first-pass effect in horses than dogs, not less than man. So it is reasonable that optimal dosage in horses is much higher than that of man [4,11]. Meanwhile, orally-administered M-1 enhanced gastric emptying of a semisolid meal and of a resin pellet meal in rats, and the potency was equal to or slightly less than that of the unchanged drug [12].…”

“…of 5 mg mosapride in man is equall to that following after single oral dosing of 0.5 mg/kg mosapraide in horses [7]. Considering about this, it is reasonable that the administration of 0.5 mg/kg mosapride showed the prokinetic effect on horse gastric emptying rates [4]. The therapeutic dosage regimen of mosapride citrate in man is 5 mg, three times a day.…”

“…Mosapride citrate, a selective 5-HT 4 receptor agonist, is a gastroprokinetic agent used clinically in the treatment of human with gastrointestinal motility dysfunctions in Japan [3]. In horses, it has been reported that oral administration of mosapride citrate can promote motility in the small intestine and cecum [4,9]. However, the pharmacokinetics of mosapride citrate in horses has not been cleared.…”