title: Modeling and simulation of orlistat to predict weight loss and weight maintenance in obesity patients.
abstract: Orlistat is used clinically worldwide as anti-obesity drug. It is a chemically synthesized hydrogenated derivative of lipstatin and is an inhibitor of gastric and pancreatic lipases. It has been found to reduce the absorption of dietary fat in the gastrointestinal tract. Modeling and simulation based on pharmacokinetic/pharmacodynamic analysis is becoming increasingly used in the design of clinical trials to assure that the trials are of high quality and are conducted efficiently. We developed a clinical trial simulation model for orlistat based on Phase III clinical study data. This innovative weight loss model includes the relationships between orlistat dose, changes in fecal fat excretion, and weight loss, and also incorporates a dropout function. The model guided the dose-finding strategy and allowed simulation of long-term clinical outcomes of orlistat.
authors.affiliation: Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd.
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Nakai
authors.forename: Russell
authors.initials: R
authors.lastname: Wada
authors.forename: Satofumi
authors.initials: S
authors.lastname: Iida
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kawanishi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Matsumoto
mesh_terms: D019440:Anti-Obesity Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects*; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D008962:Models, Theoretical; D009765:Obesity / Q000188:drug therapy*; D000077403:Orlistat; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D019440:Anti-Obesity Agents; D007783:Lactones; D000077403:Orlistat