title: Determination of influence of food intake after a single oral dose of mosapride in beagle dogs using nonlinear mixed effect modeling.
abstract: The objective of this study was to describe the population pharmacokinetics (PK) of mosapride under fasting and fed conditions. A single 5-mg oral dose of mosapride was administered to fasted (n = 15) and fed (n = 12) beagle dogs. Plasma concentrations of mosapride were subsequently measured by liquid chromatography-tandem mass spectrometry. Data were analyzed using modeling approaches with the NONMEM 7.2 software. A one-compartment open PK model utilizing model event time (MTIME) with first-order absorption and first-order elimination was found to be more appropriate than all other PK models tested. The absorption rate constants of mosapride were significantly decreased under fed conditions, compared to fasting conditions. The observed bootstrap medians of PK parameters were generally consistent with the corresponding population mean estimates. Furthermore, with the exception of some mosapride concentrations, most of observed data fell into the range of the 5th and 95th percentiles of the simulated values. Overall, the final model was able to describe the observed mosapride concentrations reasonably well. These findings suggest that food intake affects both the rate and extent of absorption of mosapride and that the pharmacological effect of mosapride can differ significantly depending on food intake.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Korea.
authors.forename: J-W
authors.initials: JW
authors.lastname: Chae
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Korea.|LG Life Sciences, Drug Metabolism and Pharmacokinetics, Daejeon, Korea.
authors.forename: J-A
authors.initials: JA
authors.lastname: Hwang
authors.affiliation: College of Pharmacy, Kyungsung University, Busan, Korea.
authors.forename: I-H
authors.initials: IH
authors.lastname: Baek
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Pradhan
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Korea.
authors.forename: B
authors.initials: B
authors.lastname: Song
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Korea.
authors.forename: H-M
authors.initials: HM
authors.lastname: Back
authors.affiliation: R&D Center Biology & Clinical Pharmacology, Samyang Biopharmaceuticals Corporation, Daejeon, Korea.
authors.forename: M
authors.initials: M
authors.lastname: Yun
authors.affiliation: Nanobio Convergence Studies, Catholic University, Bucheon, Korea.
authors.forename: C
authors.initials: C
authors.lastname: Pai
authors.affiliation: Graduate School of Clinical Pharmacy, Sookmyung Women's University, Seoul, Korea.
authors.forename: J S
authors.initials: JS
authors.lastname: Bang
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Korea.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Yun
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, Korea.
authors.forename: W
authors.initials: W
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Korea.
authors.forename: K-I
authors.initials: KI
authors.lastname: Kwon
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D004285:Dogs; D004435:Eating; D005215:Fasting; D008297:Male; D008954:Models, Biological; D009025:Morpholines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry
chemical_list: D001549:Benzamides; D009025:Morpholines; D017366:Serotonin Receptor Agonists; C062720:mosapride