Preclinical Pharmacokinetic Evaluation Of Alofanib For Cancer Treatment

Alofanib (RPT835) is a novel allosteric FGFR2 inhibitor with activity in FGFR2-expressing cancers. Here we explore the pharmacokinetic (PK) profile of compound. Five preclinical PK studies were conducted. In Study 1, alofanib was administered to 49 male BALB/C mice via two routes (oral and iv). Mice in group 1 received a single iv injection of the alofanib (30 mg/kg), while mice in group 2 received a single dose (30 mg/kg) via oral gavage. The aim of Study 2 was to evaluate the PK in 24 male Sprague Dawley rats after a single iv dose of 22 mg/kg and oral dosing in capsules at three dose levels (22, 110, and 220 mg/kg). In Study 3, PK of pharmaceutical form of alofanib in male Sprague Dawley rats after a single iv dose of 55.3, 113.8 and 218.7 mg/kg was evaluated. Studies 4 and 5 compared PK profile for alofanib in male Sprague Dawley rats after a single intraduodenal (i.d.) and subcutaneous (s.c.) dosing at 29 and 145 mg/kg. Six animals per dose group were dosed, with plasma samples collected from the tail vein up to 24 hours. Plasma concentrations were quantified by LC-MS/MS using a research qualified method. The PK data are summarized in Table. NC - Parameter cannot be calculated Following oral administration, alofanib appeared rapidly in plasma but could not be detected after 2 hours. Bioavailability for oral administration is estimated to be low ( Citation Format: Ilya Tsimafeyeu, Mikhail Byakhov, Vlatka Bencetic Mihaljevic, Jasna Padovan, Genoveva Murillo, Nadezhda Dragun, Evgenia Gavrilova, Sergei Tjulandin. Preclinical pharmacokinetic evaluation of alofanib for cancer treatment [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B084.