Preparation of cefquinome sulfate proliposome and its pharmacokinetics in rabbit

ABSTRACT

Cefquinome Sulfate [CS] is a fourth-generation cephalosporin, which has been developed solely for veterinary use. It shows potent antibacterial activity against a broad spectrum of bacterial species. However, Cefquinome is susceptible to hydrolysis, which limiting its clinical employment efficacies to some extent. So, in this study, to increase Cefquinome Sulfate biological half-life, a novel Cefquinome Sulfate proliposome was prepared by solid dispersion and effervescent techniques and characterized for morphology, particle size, entrapment efficiency and in vitro release. A Reversed Phase-High Performance Liquid Chromatography [RP-HPLC] method was first chosen and established to determine the drug concentration in plasma after intra muscular [IM] administrating Cefquinome Sulfate solution and liposome at a single dosage of 18 mg/kg in rabbit. Then their pharmacokinetics in vivo was compared. Results showed that the received liposome was milky white suspension, spherical or ellipsoidal in shape. The mean particle size was 203 +/- 5 nm and the entrapment efficiency was 53.5 +/- 0.16%. The cefaquinom sulfate solution and liposome both followed a two compartment model, in vivo. The pharmacokinetic parameters for the solution and liposomal formulations were measured as follows t[1/a alpha] were [1.214 +/- 0.135] h and [1.395 +/- 0.113] h, t[1/2beta] were [8.752 +/- 0.846] h and [16.503 +/- 1.275] h, AUC[0-24] were [49.582 +/- 9.173] [mg-h]/L and [138.727 +/- 11.034] [mg-h]/L, CL/F were [0.357 +/- 0.015] L/[h-kg] and [0.127 +/- 0.012] L/[h-kg], MRT[0-24] were [2.68 +/- 0.229] h and [5.945 +/- 0.479] h, respectively. It could be clearly seen that t[1/2beta] of liposome prolonged [p < 0.05], AUC and MRT both increased remarkably [p < 0.01], CL/F decreased. Results indicated that this preparation has more residence time and exhibits some, sustained-release tendency