ArticleAntimicrobial agents and chemotherapy2000
Compartmental pharmacokinetics and tissue distribution of multilamellar liposomal nystatin in rabbits.
Article in Antimicrobial agents and chemotherapy, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 28 citations in OpenAlex.
- Liposomal nystatin in patients with invasive aspergillosis refractory to or intolerant of amphotericin B.Antimicrobial agents and chemotherapy · 2004Trial
- A rationally designed injury kidney targeting peptide library and its application in rescuing acute kidney injury.Science advances · 2025Article
- Efficacy of Liposomal Nystatin in a Rabbit Model of Cryptococcal Meningitis.Journal of fungi (Basel, Switzerland) · 2024Article
- Spatial mapping of drug delivery to brain tissue using hyperspectral spatial frequency-domain imaging.Journal of biomedical optics · 2014Article
- Inhibition of Candida albicans biofilm formation by antimycotics released from modified polydimethyl siloxane.Mycopathologia · 2010Article
- Comparative analysis of amphotericin B lipid complex and liposomal amphotericin B kinetics of lung accumulation and fungal clearance in a murine model of acute invasive pulmonary aspergillosis.Antimicrobial agents and chemotherapy · 2007Article
- Comparative drug disposition, urinary pharmacokinetics, and renal effects of multilamellar liposomal nystatin and amphotericin B deoxycholate in rabbits.Antimicrobial agents and chemotherapy · 2003Article
- 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
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The plasma pharmacokinetics of multilamellar liposomal nystatin were studied in normal, catheterized rabbits after single and multiple daily intravenous administration of dosages of 2, 4, and 6 mg/kg of body weight, and drug levels in tissues were assessed after multiple dosing. Concentrations of liposomal nystatin were measured as those of nystatin by a validated high-performance liquid chromatography method, and plasma concentration data were fitted into a two-compartment open model. Across the investigated dosage range, liposomal nystatin demonstrated nonlinear kinetics with more than proportional increases in the AUC(0-24) and decreasing clearance, consistent with dose-dependent tissue distribution and/or a dose-dependent elimination process. After single-dose administration, the mean C(max) increased from 13.07 microg/ml at 2 mg/kg to 41.91 microg/ml at 6 mg/kg (P < 0.001); the AUC(0-24) changed from 11.65 to 67.44 microg. h/ml (P < 0.001), the V(d) changed from 0.205 to 0. 184 liters/kg (not significant), the CL(t) from 0.173 to 0.101 liters/kg. h (P < 0.05), and terminal half-life from 0.96 to 1.51 h (P < 0.05). There were no significant changes in pharmacokinetic parameters after multiple dosing over 14 days. Assessment of tissue concentrations of nystatin near peak plasma levels after multiple dosing over 15 days revealed preferential distribution to the lungs, liver, and spleen at that time point. Substantial levels were also found in the urine, raising the possibility that renal excretion may play a significant role in drug elimination. Liposomal nystatin administered to rabbits was well tolerated and displayed nonlinear pharmacokinetics, potentially therapeutic peak plasma concentrations, and substantial penetration into tissues. Pharmacokinetic parameters were very similar to those observed in patients, thus validating results derived from infection models in the rabbit and allowing inferences to be made about the treatment of invasive fungal infections in humans.
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