Cabanes A, Reig F, Garcia-Anton J M, Arboix M
Department of Peptides, CID, CSIC, Barcelona, Spain.
Res Vet Sci. 1998 May-Jun;64(3):213-7. doi: 10.1016/s0034-5288(98)90128-x.
Gentamycin sulphate (GS) and gentamycin oleate (GO) were encapsulated in liposomes composed of phosphatidylcholine (HPC) and cholesterol (CHOL) (molar ratio 7:7:2 and 5:5:1, respectively), and were administered via intramuscular injection to rabbits, to evaluate their potential use as sustained release formulations. Five groups of five animals each were used for the pharmacokinetic study, and treatments were established as follows: 3 mg kg(-1) of GS i.v., 3 mg kg(-1) of GS i.m., 3 mg kg(-1) of liposome-containing gentamycin sulphate (LGS) i.m., 3 mg kg(-1) of GO i.m., and 3 mg kg(-1) of liposome-containing gentamycin oleate (LGO) i.m. Gentamycin plasma concentrations after i.m. administration of LGS were extremely low compared with those obtained after the i.m. administration of GS; the peak plasma concentration (Cmax) showed an eight-fold decrease with LGS, and the area under the concentration-time curve (AUC) was four-fold lower for the liposomal form. The apparent elimination half-life estimated after administration of LGS showed a three-fold increase compared with values calculated for free GS. After the administration of the same dose of LGO, Cmax obtained showed a 2.5-fold decrease in relation to peak concentrations of free GO, and the apparent beta-half life of encapsulated GO showed a three-fold increase compared with i.m. GO. Large-size liposomes containing gentamycin administered i.m. to rabbits gave sustained drug release from the injection site, providing prolonged plasma concentrations of the drug in the body.
将硫酸庆大霉素（GS）和油酸庆大霉素（GO）包裹于由磷脂酰胆碱（HPC）和胆固醇（CHOL）组成的脂质体中（摩尔比分别为7:7:2和5:5:1），通过肌肉注射给予兔子，以评估它们作为缓释制剂的潜在用途。每组五只动物，共五组用于药代动力学研究，处理方式如下：静脉注射3mg kg⁻¹的GS，肌肉注射3mg kg⁻¹的GS，肌肉注射3mg kg⁻¹含硫酸庆大霉素的脂质体（LGS），肌肉注射3mg kg⁻¹的GO，以及肌肉注射3mg kg⁻¹含油酸庆大霉素的脂质体（LGO）。与肌肉注射GS后相比，肌肉注射LGS后庆大霉素的血浆浓度极低；血浆峰浓度（Cmax）显示LGS降低了八倍，脂质体形式的浓度-时间曲线下面积（AUC）降低了四倍。注射LGS后估计的表观消除半衰期与游离GS计算值相比增加了三倍。给予相同剂量的LGO后，获得的Cmax相对于游离GO的峰浓度降低了2.5倍，包封的GO的表观β半衰期与肌肉注射GO相比增加了三倍。向兔子肌肉注射含庆大霉素的大尺寸脂质体可使药物从注射部位持续释放，从而使药物在体内的血浆浓度延长。
