Non-clinical studies indicating lack of interactions between iron/calcium ions and linzagolix, an orally available GnRH antagonist
Creators: name: Kobayashi, Kaoru
name: Tezuka, Motohiro
name: Toyoda, Yasuyuki
name: Kurooka, Takao
name: Oota, Emiko
name: Tamai, Yasuaki
name: Abe, Yoshikazu
name: Kiguchi, Sumiyoshi
name: Endo, Takuro
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Biophysics
subject: Biochemistry
subject: Medicine
subject: Pharmacology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: 69999 Biological Sciences not elsewhere classified
subject: FOS: Biological sciences
subject: Cancer
subject: 110309 Infectious Diseases
subject: FOS: Health sciences

description: Linzagolix is an orally available gonadotropin-releasing hormone antagonist used to treat sex-hormone-dependent diseases in women. This study aimed to investigate drug-drug interactions between linzagolix and iron/calcium ions in the intended clinical setting by conducting pharmacokinetic studies <i>in vitro</i> and in rats.Insoluble precipitate formation with metal ions was evaluated by measuring linzagolix concentrations in four types of bio-relevant dissolution media (fasted/fed state simulated gastric fluid and fasted/fed state simulated gastric fluid version 2), and chelate complex formation with metal ions was evaluated by release of linzagolix from a cellulose membrane sac. In these <i>in vitro</i> studies, linzagolix showed no potential for insoluble precipitate formation under fasted/fed conditions and no chelate complex formation in the presence of metal ions.In rats, the plasma concentration-time profiles of linzagolix and iron ion were similar regardless of whether they were administered with or without ferrous sulphate and linzagolix choline at clinically relevant doses. Thus, linzagolix and iron ion had no effect on each other’s absorption <i>in vivo</i>.In conclusion, linzagolix is unlikely to cause clinically relevant drug-drug interactions by chelating metal ions according to the results of <i>in vitro</i> and <i>in vivo</i> studies. Linzagolix is an orally available gonadotropin-releasing hormone antagonist used to treat sex-hormone-dependent diseases in women. This study aimed to investigate drug-drug interactions between linzagolix and iron/calcium ions in the intended clinical setting by conducting pharmacokinetic studies <i>in vitro</i> and in rats. Insoluble precipitate formation with metal ions was evaluated by measuring linzagolix concentrations in four types of bio-relevant dissolution media (fasted/fed state simulated gastric fluid and fasted/fed state simulated gastric fluid version 2), and chelate complex formation with metal ions was evaluated by release of linzagolix from a cellulose membrane sac. In these <i>in vitro</i> studies, linzagolix showed no potential for insoluble precipitate formation under fasted/fed conditions and no chelate complex formation in the presence of metal ions. In rats, the plasma concentration-time profiles of linzagolix and iron ion were similar regardless of whether they were administered with or without ferrous sulphate and linzagolix choline at clinically relevant doses. Thus, linzagolix and iron ion had no effect on each other’s absorption <i>in vivo</i>. In conclusion, linzagolix is unlikely to cause clinically relevant drug-drug interactions by chelating metal ions according to the results of <i>in vitro</i> and <i>in vivo</i> studies.