Pharmaceutical Research

, Volume 15, Issue 11, pp 1775–1781

Altered Tissue Distribution and Elimination of Amikacin Encapsulated in Unilamellar, Low-Clearance Liposomes (MiKasome®)

  • Robert M. Fielding
  • Ramilla O. Lewis
  • Lotus Moon-McDermott

DOI: 10.1023/A:1011925132473

Cite this article as:
Fielding, R.M., Lewis, R.O. & Moon-McDermott, L. Pharm Res (1998) 15: 1775. doi:10.1023/A:1011925132473


Purpose. Amikacin in small unilamellar liposomes (MiKasome®) has prolonged plasma residence (half-life > 24hr) and sustained efficacy in Gram-negative infection models. Since low-clearance liposomes may be subject to a lower rate of phagocytic uptake, we hypothesized this formulation may enhance amikacin distribution to tissues outside the mononuclear phagocyte system.

Methods. Rats received one intravenous dose (50 mg/kg) of conventional or liposomal amikacin. Amikacin was measured for ten days in plasma, twelve tissues, urine and bile.

Results. Liposomal amikacin increased and prolonged drug exposure in all tissues. Tissue half-lives (63−465 hr) exceeded the plasma half-life (24.5 hr). Peak levels occurred within 4 hours in some tissues, but were delayed 1−3 days in spleen, liver, lungs and duodenum, demonstrating the importance of characterizing the entire tissue concentration vs. time profile for liposomal drugs. Predicted steady-state tissue concentrations for twice weekly dosing were >100 μg/g. Less than half the liposomal amikacin was recovered in tissues and excreta, suggesting metabolism occurred. Amikacin was not detected in plasma ultrafiltrates. Tissue-plasma partition coefficients (0.2-0.8 in most tissues) estimated from tissue-plasma ratios at Tmax were similar to those estimated from tissue AUCs.

Conclusions. Low-clearance liposomal amikacin increased and prolonged drug residence in all tissues compared to conventional amikacin. The long tissue half-lives suggest liposomal amikacin is sequestered within tissues, and that an extended dosing interval is appropriate for chronic or prophylactic therapy with this formulation.

liposomesaminoglycosidesamikacinMiKasometissue distributionelimination/excretion

Copyright information

© Plenum Publishing Corporation 1998

Authors and Affiliations

  • Robert M. Fielding
    • 1
  • Ramilla O. Lewis
    • 2
  • Lotus Moon-McDermott
    • 2
  1. 1.Biologistic ServicesBoulder
  2. 2.Biopharmaceutics GroupNeXstar Pharmaceuticals, Inc.Boulder