ArticleAntimicrobial agents and chemotherapy2002
Pharmacokinetics and efficacies of liposomal and conventional formulations of tobramycin after intratracheal administration in rats with pulmonary Burkholderia cepacia infection.
Article in Antimicrobial agents and chemotherapy, 2002. 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, 33 citations in OpenAlex.
- Drug delivery strategies for antibiofilm therapy.Nature reviews. Microbiology · 2023Review
- Tobramycin Nanoantibiotics and Their Advantages: A Minireview.International journal of molecular sciences · 2022Review
- Medicinal Chemistry of Inhibitors Targeting Resistant Bacteria.Current topics in medicinal chemistry · 2022Article
- Coating of a Novel Antimicrobial Nanoparticle with a Macrophage Membrane for the Selective Entry into Infected Macrophages and Killing of Intracellular Staphylococci.Advanced functional materials · 2020Article
- Lipid-Based Antimicrobial Delivery-Systems for the Treatment of Bacterial Infections.Frontiers in chemistry · 2019Review
- Current Trends in Development of Liposomes for Targeting Bacterial Biofilms.Pharmaceutics · 2016Review
- Nanotechnology and pulmonary delivery to overcome resistance in infectious diseases.Advanced drug delivery reviews · 2013Review
- Intratracheal versus intravenous liposomal delivery of siRNA, antisense oligonucleotides and anticancer drug.Pharmaceutical research · 2009Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The objective of the present study was to determine the pharmacokinetics and efficacies of liposomal and conventional formulations of tobramycin against Burkholderia cepacia in a model of chronic lung infection. Male Sprague-Dawley rats were inoculated intratracheally with 10(6) CFU of a very resistant strain of B. cepacia (strain BC 1368; MIC, 128 micro g/ml) to establish lung infection. A 1,200- micro g dose of tobramycin was administered intratracheally as a liposomal formulation and as a conventional formulation. Rats were anesthetized and exsanguinated by cardiac puncture at different times over 24 h to assess pulmonary tobramycin concentrations and the number of residual CFU. Pharmacokinetic parameters were calculated by using a two-compartment model with NONMEM. The mean half-life at the beta phase (t(1/2beta)) and the pulmonary exposure (the area under the concentration-time curve [AUC]) of liposomal tobramycin were 19.7 h (coefficient of variation [CV], 24.2%) and 6,811 micro g. h/lungs (CV, 19.7%), respectively. The pharmacokinetics of conventional tobramycin were statistically different, with a t(1/2beta) and AUC of 12.9 h (CV, 31.4%) and 821 micro g. h/lungs (CV, 15.0%), respectively. Pearson chi-square analyses were performed on residual CFU data distributed in the following categories: <10(3), 10(3) to 10(5), and >10(5). Differences in CFU data between formulations showed a statistical trend (P < 0.10) when data from all time points were used, and statistically significant differences were found after 12 h (P < 0.05), with greater eradication achieved with the liposomal formulation. In conclusion, intratracheal administration of tobramycin in liposomes was associated with marked changes in the pharmacokinetics of the drug in the lung and an apparent trend for a prolonged efficacy against B. cepacia. These results support the hypothesis that inhalation of liposomal tobramycin may improve the management of chronic pulmonary infections caused by resistant bacteria in patients with cystic fibrosis.
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