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Cited by 72Antibiotics Pharmacokinetics and EfficacyNanoparticle-Based Drug DeliveryAdvanced Drug Delivery Systems

The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.

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

Fielding, Robert M., Lewis, Ramilla O., Moon-McDermott, Lotus·1998·Pharmaceutical Research
DOI 10.1023/a:1011925132473
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Abstract

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 microg/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.

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Crossref · 10.1023/a:1011925132473

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Research works printed but not linked: 3

  1. E. T. Eng. Prophylactic and therapeutic treatment of Gram-negative septicemia with liposomal and non-liposomal encapsulated amikacin in immunocompromized mice. Thesis presented to California State Polytechnic University, Pomona, CA, 1996.
  2. W. J. Jusko. Guidelines for collection and analysis of pharmacokinetic data. In W. E. Evans et al. (eds.), Applied Pharmacokinetics, 3rd edition. Applied Therapeutics, Inc., Vancouver, WA, 1992, Chapter 2.
  3. R. M. Fielding, B. Feistner, L. Moon-McDermott, S. C. Gill, D. Roamer, and R. A. Bendele. Liposomal amikacin (Mikasome®): reduced clearance and volume of distribution in rats. Pharm. Res. 13:S-479 (1996).

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Metadata

Authors
Fielding, R. M., Lewis, R. O., & Moon-McDermott, L.
Corresponding author
Fielding, Robert M.
ORCID
Fielding, Robert M.
Venue
Pharmaceutical Research
Publisher
Springer Science and Business Media LLC
Published
1998-11
Volume
15
Issue
11
Pages
1775-1781
ISSN
  • 0724-8741 (ISSN-L)
  • 1573-904X
DOI
10.1023/a:1011925132473
OpenAlex
W2191567995
Cited by
72
References
19
Citations by year
2026: 2 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 3 · 2019: 5 · 2018: 2 · 2017: 3 · 2014: 1 · 2013: 1 · 2012: 2
FWCI
3.42
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Pharmaceutical Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Antibiotics Pharmacokinetics and Efficacy
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Keywords
amikacin, liposomal amikacin, unilamellar liposomes, tissue distribution, drug elimination, phagocytic uptake, extended dosing interval, aminoglycosides, gram-negative bacterial infection
MeSH terms
Amikacin, Animals, Drug Carriers, Liposomes, Male, Metabolic Clearance Rate, Tissue Distribution, Rats, Sprague-Dawley, Rats

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