ArticlePharmaceutical research2000
Safety, toxicokinetics and tissue distribution of long-term intravenous liposomal amphotericin B (AmBisome): a 91-day study in rats.
Article in Pharmaceutical research, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 61 citations in OpenAlex.
- High-dose weekly liposomal amphotericin B antifungal prophylaxis following reduced-intensity conditioning allogeneic stem cell transplantation.Bone marrow transplantation · 2007Trial
- High-dose weekly AmBisome antifungal prophylaxis in pediatric patients undergoing hematopoietic stem cell transplantation: a pharmacokinetic study.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2006Trial
- Pharmacokinetics, excretion, and mass balance of liposomal amphotericin B (AmBisome) and amphotericin B deoxycholate in humans.Antimicrobial agents and chemotherapy · 2002Trial
- Optimizing antifungal dosing for invasiveFrontiers in pharmacology · 2025Article
- Polyene Antibiotics Physical Chemistry and Their Effect on Lipid Membranes; Impacting Biological Processes and Medical Applications.Membranes · 2022Review
- Case report: Reversible encephalopathy associated with liposomal amphotericin B in a patient with cryptococcal meningitis.Frontiers in neurology · 2022Article
- Therapeutic Challenges of Non-Antimicrobial agents and chemotherapy · 2019Review
- Exploiting knowledge on pharmacodynamics-pharmacokinetics for accelerated anti-leishmanial drug discovery/development.Expert opinion on drug metabolism & toxicology · 2019Review
- Preclinical Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antifungal Activity of Liposomal Amphotericin B.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Review
- Clinical Pharmacokinetics, Pharmacodynamics, Safety and Efficacy of Liposomal Amphotericin B.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Review
- Pharmacology of Liposomal Amphotericin B: An Introduction to Preclinical and Clinical Advances for Treatment of Life-threatening Invasive Fungal Infections.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
- Lipsosomal amphotericin B: a review of its properties, function, and use for treatment of cutaneous leishmaniasis.Research and reports in tropical medicine · 2019Article
- Review
- Tissue penetration of antifungal agents.Clinical microbiology reviews · 2014Review
- Secondary Antifungal Prophylaxis in Hematopoietic Stem Cell Transplantation (HSCT)/Acute Leukemia Patients.Current infectious disease reports · 2011Article
- Central nervous system toxicity associated with liposomal amphotericin B therapy for cutaneous leishmaniasis.The American journal of tropical medicine and hygiene · 2011Article
- Comparative efficacies, toxicities, and tissue concentrations of amphotericin B lipid formulations in a murine pulmonary aspergillosis model.Antimicrobial agents and chemotherapy · 2006Article
- Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins.Antimicrobial agents and chemotherapy · 2002Article
- Relationship of pharmacokinetically-calculated volumes of distribution to the physiologic distribution of liposomal drugs in tissues: implications for the characterization of liposomal formulations.Pharmaceutical research · 2001Article
- Amphotericin B Pharmacokinetics: Inter-strain Differences in Rats Following Intravenous Administration of the Most Commonly Marketed Formulations of the Drug.Iranian journal of pharmaceutical research : IJPRArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAmphotericin B in small, unilamellar liposomes (AmBisome) is safer and produces higher plasma concentrations than other formulations. Because liposomes may increase and prolong tissue exposures, the potential for drug accumulation or delayed toxicity after chronic AmBisome was investigated.
methodsRats (174/sex) received intravenous AmBisome (1, 4, or 12 mg/kg), dextrose, or empty liposomes for 91 days with a 30-day recovery. Safety (including clinical and microscopic pathology) and toxicokinetics in plasma and tissues were evaluated.
resultsChemical and histopathologic changes demonstrated that the kidneys and liver were the target organs for chronic AmBisome toxicity. Nephrotoxicity was moderate (urean nitrogen [BUN] < or = 51 mg/dl; creatinine unchanged). Liposome-related changes (vacuolated macrophages and hypercholesterolemia) were also observed. Although plasma and tissue accumulation was nonlinear and progressive (clearance and volume decreased, half-life increased with dose and time), most toxic changes occurred early, stabilized by the end of dosing, and reversed during recovery. There were no delayed toxicities. Concentrations in liver and spleen greatly exceeded those in plasma: kidney and lung concentrations were similar to those in plasma. Elimination half-lives were 1-4 weeks in all tissues.
conclusionsDespite nonlinear accumulation, AmBisome revealed predictable hepatic and renal toxicities after 91 days, with no new or delayed effects after prolonged treatment at high doses that resulted in plasma levels >200 microg/ml and tissue levels >3000 microg/g.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.