Fu Qiang, Fu Hua-Lin, Huan Luo, Zhang Wei, Shu Guang, Liu Meng-Jiao, Deng Feng-Ying, Hu Jun
Department of Pharmacy, College of Veterinary Medicine, Sichuan Agriculture University, Ya, an, Sichuan, 625014,China.
Iran J Pharm Res. 2013 Fall;12(4):611-21.
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: t1/2 α were (1.214 ± 0.135) h and (1.395 ± 0.113) h, t1/2 β 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 t1/2 β 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.
硫酸头孢喹肟（CS）是一种第四代头孢菌素，专为兽用而研发。它对多种细菌具有强大的抗菌活性。然而，头孢喹肟易水解，这在一定程度上限制了其临床应用效果。因此，在本研究中，为提高硫酸头孢喹肟的生物半衰期，采用固体分散和泡腾技术制备了一种新型硫酸头孢喹肟前体脂质体，并对其形态、粒径、包封率和体外释放进行了表征。首先选择并建立了反相高效液相色谱（RP-HPLC）法，以测定兔单次肌内注射（IM）18mg/kg硫酸头孢喹肟溶液和脂质体后血浆中的药物浓度。然后比较了它们在体内的药代动力学。结果表明，所制备的脂质体为乳白色混悬液，形状为球形或椭圆形。平均粒径为203±5nm，包封率为53.5±0.16%。硫酸头孢喹肟溶液和脂质体在体内均符合二室模型。溶液剂和脂质体制剂的药代动力学参数测定如下：t1/2α分别为(1.214±0.135)h和(1.395±0.113)h，t1/2β分别为(8.752±0.846)h和(16.503±1.275)h，AUC(0-24)分别为(49.582±9.173)(mg·h)/L和(138.727±11.034)(mg·h)/L，CL/F分别为(0.357±0.015)L/(h·kg)和(0.127±0.012)L/(h·kg)，MRT(0-24)分别为(2.68±0.229)h和(5.945±0.479)h。可以清楚地看到，脂质体的t1/2β延长（p<0.05），AUC和MRT均显著增加（p<0.01），CL/F降低。结果表明，该制剂具有更长的驻留时间，并呈现出一定的缓释趋势。
