Pharmacokinetics and protein binding of MPT0B292

ABSTRACT MPT0B292 was identified through screening of compounds able to selectively acetylate α‐tubulins in cells and exhibited potent anti‐tumor, anti‐angiogenesis and anti‐metastatic effects in vitro and in vivo. Because of poor water solubility, MPT0B292 is difficult to formulate with conventional approaches and hence difficulties are experienced in research practices. We mixed MPT0B292 with albumin in the aqueous solvent to form drug albumin nanoparticles with the size range around 333 nm. We investigated unbound fractions of these nanoparticles in different or same albumin concentration solutions. Unlike most drugs, the binding of MPT0B292 in human serum albumin increased with increasing drug concentration. We also developed and validated an analytical method to determine MPT0B292 in rat plasma. This analytical method was applied successfully to the intravenous pharmacokinetic study of MPT0B292 in rats. The single dose study was regularly done to characterize the pharmacokinetic property of the drug. Additionally, we executed an IV infusion study to verify the extraction ratio of MPT0B292, which was more clever and novel than usual. The pharmacokinetic analysis revealed that MPT0B292 was a high extraction ratio drug with high systemic clearance, high volume of distribution and short half‐life in rats.
Source: Biopharmaceutics and Drug Disposition - Category: Drugs & Pharmacology Authors: Tags: Original Paper Source Type: research