Pharmacokinetics of the Gastrokinetic Agent Mosapride Citrate After Single Oral Administration in Horses
Mosapride citrate, a selective 5-HT4 receptor agonist, is a gastrokinetic agent used clinically in the treatment of patients with gastrointestinal motility dysfunctions in Japan. In horses, it has been reported that oral administration of mosapride citrate can promote motility in the small intestine and cecum. However, the pharmacokinetics of mosapride citrate has not been cleared. In this study, we report mosapride citrate pharmacokinetic data obtained following after single oral doses.
Seven healthy thoroughbreds (1 mare and 6 geldings) were dosed with 1,000 ml of distilled water and 0.5 mg/kg, 1.0 mg/kg, or 1.5 mg/kg mosapride citrate (Dainippon Sumitomo Pharma, Japan) through a nasogastric tube. The study was conducted as a Latin-square design; thus, each horse received each dosage. There was a 1-week washout period between subsequent treatments. Jugular venous blood was collected just before mosapride administration and at 15, 30, 60, 120, 180, 360, 480 minutes after dosing. Serum mosapride concentrations were measured by a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method.
Mean serum levels of mosapride reach the maximum 60-120 minutes after administration, with levels of 0.029 ± 0.004, 0.047 ± 0.007, 0.101 ± 0.014 µg/ml at doses of 0.5, 1.0, 1.5 mg/kg, respectively. Thereafter, serum levels of mosapride decreased with t1/2s of 185-233 minutes. Mosapride showed the Cmaxs of 0.031 ± 0.004, 0.060 ± 0.009, 0.104 ± 0.012 µg/ml and AUC0-480s of 7.6 ± 1.0, 15.1 ± 2.1, 25.7 ± 3.1 µg/ml.min at doses of 0.5, 1.0, 1.5 mg/kg, respectively. The Cmax and AUC0-480 increased in proportion to the dose, indicating linear pharmacokinetics of mosapride up to 1.5 mg/kg.
The pharmacokinetic profiles of mosapride in horses are quite different from that in humans. The average t1/2 in horses in this study was almost 2 fold longer than the 2.0 hours reported in healthy adult humans. Therefore, it is thought that it is suitable to reduce the number of doses a day in horses to half. In humans, the therapeutic dosage regimen of mosapride citrate is 5 mg, three times a day. Mean while, it has been reported that the optimal orally administered dosage of mosapride citrate in horses is 1.5 to 2 mg/kg. Therefore, it arrives at the following conclusions: the predicted therapeutic dosage regimen of mosapride citrate in horses is 1.5 to 2 mg/kg, a time or two times a day.