Pharmacokinetics and protein binding of MPT0B292

Yu En Tien, Chan Jung Li, Jing Ping Liou, Jang-Yang Chang, Jin Ding Huang

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)340-350
Number of pages11
JournalBiopharmaceutics and Drug Disposition
Volume38
Issue number5
DOIs
Publication statusPublished - 2017 Jul 1

Fingerprint

Protein Binding
Pharmacokinetics
Albumins
Pharmaceutical Preparations
Nanoparticles
Tubulin
Serum Albumin
Solubility
Half-Life
Water
Research
Neoplasms

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

Cite this

Tien, Yu En ; Li, Chan Jung ; Liou, Jing Ping ; Chang, Jang-Yang ; Huang, Jin Ding. / Pharmacokinetics and protein binding of MPT0B292. In: Biopharmaceutics and Drug Disposition. 2017 ; Vol. 38, No. 5. pp. 340-350.
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Pharmacokinetics and protein binding of MPT0B292. / Tien, Yu En; Li, Chan Jung; Liou, Jing Ping; Chang, Jang-Yang; Huang, Jin Ding.

In: Biopharmaceutics and Drug Disposition, Vol. 38, No. 5, 01.07.2017, p. 340-350.

Research output: Contribution to journalArticle

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