title: Pharmacokinetics and protein binding of MPT0B292.
abstract: MPT0B292 was identified through screening of compounds able selectively to acetylate α-tubulins in cells and it exhibited potent anti-tumor, anti-angiogenesis and anti-metastatic effects in vitro and in vivo. Because of its poor water solubility, MPT0B292 is difficult to formulate with conventional approaches and hence difficulties are experienced in research practices. MPT0B292 was mixed with albumin in an aqueous solvent to form drug albumin nanoparticles with a size range around 333 nm. Unbound fractions of these nanoparticles were investigated in different or the same albumin concentration solutions. Unlike most drugs, the binding of MPT0B292 in human serum albumin increased with increasing drug concentrations. An analytical method was also developed and validated to determine MPT0B292 in rat plasma. This analytical method was applied successfully to the intravenous pharmacokinetic study of MPT0B292 in rats. A single dose study was regularly done to characterize the pharmacokinetic properties of the drug. Additionally, a novel i.v. infusion study was carried out to verify the extraction ratio of MPT0B292. The pharmacokinetic analysis revealed that MPT0B292 was a high extraction ratio drug with high systemic clearance, a high volume of distribution and a short half-life in rats. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Departments of Clinical Pharmacy and Pharmaceutical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-En
authors.identifier: http://orcid.org/0000-0001-5563-042X
authors.initials: YE
authors.lastname: Tien
authors.affiliation: Departments of Clinical Pharmacy and Pharmaceutical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chan-Jung
authors.initials: CJ
authors.lastname: Li
authors.affiliation: School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jang-Yang
authors.initials: JY
authors.lastname: Chang
authors.affiliation: Departments of Clinical Pharmacy and Pharmaceutical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jin-Ding
authors.initials: JD
authors.lastname: Huang
mesh_terms: D000418:Albumins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011083:Polycyclic Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D011485:Protein Binding; D017207:Rats, Sprague-Dawley; D050257:Tubulin Modulators / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000418:Albumins; D000970:Antineoplastic Agents; C000626811:MPT0B292; D011083:Polycyclic Compounds; D050257:Tubulin Modulators
keywords: MPT0B292; disposition; human serum albumin; pharmacokinetic; protein binding