EVALUATION OF FREE AND LIPOSOME-ENCAPSULATED GENTAMICIN FOR INTRAMUSCULAR SUSTAINED-RELEASE IN RABBITS

Gentamycin sulphate (Gs) and gentamycin oleate (Go) were encapsulated in liposomes composed of phosphatidylcholine (HPC) and cholesterol (CH OL) (molar ratio 7:7:2 and 5.5.1, respectively), and were administered via intramuscular injection to rabbits, to evaluate their potential u se as sustained release formulations. Five groups of five animals each were used for the pharmacokinetic study, and treatments were establis hed as follows: 3 mg kg(-1) of GS i.v., 3 mg kg(-1) of GS i.m., 3 mg k g(-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 oleat e (LGO) i.m. Gentamycin plasma concentrations after i.m. administratio n of LGS were extremely low compared with those obtained after the i.m . administration of GS; the peak plasma concentration (c(max)) 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 appar ent elimination half-life estimated after administration of LGs showed a three-fold increase compared with values calculated for free Gs. Af ter the administration of the same dose of LGO, c(max) obtained showed a 2.5-fold decrease in relation to peak concentrations of free Go, an d the apparent a-half life of encapsulated Go showed a three-fold incr ease compared with i.m. Go. Large-size liposomes containing gentamycin administered i.m. to rabbits gave sustained drug release from the inj ection site, providing prolonged plasma concentrations of the drug in the body.