A pharmacokinetic and pharmacodynamic evaluation of colchicine sustained-release pellets for preventing gout

Abstract

Gout is a common metabolic disease caused by the chronic deposition of monosodium urate (MSU) crystals in joints and tissues. Low-dose of colchicine (COL) has become the first-line drug for clinical prevention of acute gout attacks. However, their high cytotoxicity leads to a narrow therapeutic index and frequent toxic reactions. This study developed colchicine sustained-release pellets (COL-SRPs) using fluidized-bed technology to overcome the shortcomings of fluctuation in blood concentration and other side effects of commercial rapid release COL preparations. The COL-SRPs showed a smooth surface and spherical shape under a scanning electron microscope (SEM). The in vitro release curves of the COL-SRPs under different pH dissolution medium were not significantly different (similarity factors 2 ˃ 50). The release of COL from pellets may be a diffuse action. Pharmacokinetic studies demonstrated that the mean residence time (MRT) and tmax of the COL-SRPs group were significantly higher than those in the commercial colchicine tablets (COL-Ts) group. Pharmacodynamic studies comprehensively evaluated serum inflammatory factor indicators (IL-1β and TNF-α), liver and kidney function indexes (ALT, AST and CRE), as well as ankle joint histopathology, further suggesting that the COL-SRPs exhibited a more optimal preventive potential against acute gout attack. The COL-SRPs prepared in this study provide a powerful alternative to commercial COL-Ts by overcoming their shortcomings and having great industrial production potential.