INTRAVITREAL PHARMACOKINETICS OF LIPOSOME-ENCAPSULATED AMIKACIN IN A RABBIT MODEL

Background. Intravitreal injection of antibiotics has become a standar d therapy for bacterial endophthalmitis. The duration of effective ant imicrobial levels in the vitreous after single injection, however, may not be long enough to get optimal response. The authors prepared lipo some-encapsulated amikacin for prolonging the duration of intravitreal therapeutic concentrations and investigated the intravitreal pharmaco kinetics of the liposomes and amikacin in phosphate buffer solution (P BS) as control. Methods: The liposome-encapsulated amikacin was prepar ed by reverse-phase evaporation method. The intravitreal pharmacokinet ics of the liposomes was compared with amikacin in PBS by fluorescence polarization immunoassay. Albino rabbits were randomly distributed in to 12 groups. Rabbits in groups 1 to 6 and in groups I to VI (control groups) received an intravitreal injection of the liposome-encapsulate d amikacin and amikacin in PBS, respectively. Results: The encapsulati on rate of amikacin was 91%. The time of 50% spontaneous degradation ( half-life) of the liposomes in PBS (38-degrees-C, pH 7.4) was 47.6 day s, and the time of 50% release (half-life) of the drug from the liposo mes in PBS was 84.8 hours. The vitreous amikacin concentrations in gro ups 1 to 6 were significantly greater (P < 0.05) than those in control groups I to VI in every time interval, except in groups 1 to 3 at 1 h our after injection. The difference was particularly obvious in the en dophthalmitis groups. The clearance of encapsulated amikacin in vitreo us appeared to be related to the state of blood-ocular barrier and to the structural integrity of vitreous. The distribution, the absorption , and the elimination of encapsulated amikacin in vitreous showed the first-order kinetics. Conclusion: The liposome-encapsulated amikacin p rolonged half-life of the drug in vitreous. The results of the pharmac okinetic analysis suggested that in endophthalmitis, especially in sev ere cases, the liposomes may be preferable to conventional preparation .