ArticleAntimicrobial agents and chemotherapy2004
Cellular pharmacokinetics and pharmacodynamics of the glycopeptide antibiotic oritavancin (LY333328) in a model of J774 mouse macrophages.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Extrapolation of oritavancin PK/PD targets to inform therapeutic drug monitoring: a systematic review.The Journal of antimicrobial chemotherapy · 2026Pooled it
- Deep Learning Enables Identification of Antimicrobial Peptides Through Mechanochromic Fingerprints.Angewandte Chemie (International ed. in English) · 2026Article
- Antibacterial Activity of Zinc-Doped Hydroxyapatite and Vancomycin-Loaded Gelatin Nanoparticles against IntracellularACS applied nano materials · 2024Article
- Strategies to Overcome Biological Barriers Associated with Pulmonary Drug Delivery.Pharmaceutics · 2022Review
- Emergence and Mechanism of Resistance of Tulathromycin AgainstFrontiers in veterinary science · 2022Article
- Current and future options for treating complicated skin and soft tissue infections: focus on fluoroquinolones and long-acting lipoglycopeptide antibiotics.The Journal of antimicrobial chemotherapy · 2021Article
- Pharmacokinetic/Pharmacodynamic Modeling of Spiramycin againstPathogens (Basel, Switzerland) · 2021Article
- Development and Preclinical Evaluation of New Inhaled Lipoglycopeptides for the Treatment of Persistent Pulmonary Methicillin-Resistant Staphylococcus aureus Infections.Antimicrobial agents and chemotherapy · 2021Article
- The PK/PD Integration and Resistance of Tilmicosin againstPathogens (Basel, Switzerland) · 2020Article
- Article
- Clinical Pharmacokinetics and Pharmacodynamics of Telavancin Compared with the Other Glycopeptides.Clinical pharmacokinetics · 2018Review
- A Phage Lysin Fused to a Cell-Penetrating Peptide Kills Intracellular Methicillin-Resistant Staphylococcus aureus in Keratinocytes and Has Potential as a Treatment for Skin Infections in Mice.Applied and environmental microbiology · 2018Article
- Cellular Pharmacokinetics and Intracellular Activity of Gepotidacin against Staphylococcus aureus Isolates with Different Resistance Phenotypes in Models of Cultured Phagocytic Cells.Antimicrobial agents and chemotherapy · 2018Article
- Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review.Drugs · 2015Review
- Prolonged Use of Oritavancin for Vancomycin-Resistant Enterococcus faecium Prosthetic Valve Endocarditis.Open forum infectious diseases · 2015Article
- Review
- Cellular pharmacokinetics and intracellular activity of the novel peptide deformylase inhibitor GSK1322322 against Staphylococcus aureus laboratory and clinical strains with various resistance phenotypes: studies with human THP-1 monocytes and J774 murine macrophages.Antimicrobial agents and chemotherapy · 2015Article
- Oritavancin for the treatment of acute bacterial skin and skin structure infections: an evidence-based review.Core evidence · 2015Review
- Temporins A and B stimulate migration of HaCaT keratinocytes and kill intracellular Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2014Article
- Study of macrophage functions in murine J774 cells and human activated THP-1 cells exposed to oritavancin, a lipoglycopeptide with high cellular accumulation.Antimicrobial agents and chemotherapy · 2014Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The intracellular pharmacokinetics and pharmacodynamics of oritavancin (LY333328) were studied in cultured cells. Oritavancin was avidly accumulated by J774 and THP-1 macrophages and rat fibroblasts and to a lesser extent by LLC-PK1 and Caco-2 cells. In J774 macrophages, the level of accumulation reached a plateau (at 370-fold the extracellular concentration) within 24 h and was partly defeated by a rise in serum protein levels. Efflux was incomplete (with a plateau at two-thirds of the original level at 6 h). In short-term kinetic studies, oritavancin uptake was linear for up to 4 h (as was the case for horseradish peroxidase and small latex beads, used as markers of the fluid phase and adsorptive endocytosis, respectively), which was in contrast to azithromycin and chloroquine uptake (which accumulate in cells by diffusion and segregation). The rates of clearance of oritavancin and latex beads were comparable (150 and 120 microl x mg of protein(-1) x h(-1), respectively) and were approximately 200 times higher than that of horseradish peroxidase. Oritavancin accumulation was partially reduced by monensin but was unaffected by acidic pH (these conditions abolished chloroquine accumulation). Cell-associated oritavancin was found in lysosomal fractions after homogenization of J774 macrophages and fractionation by isopycnic centrifugation. Oritavancin was bactericidal against intracellular Staphylococcus aureus (phagolysosomal infection) but was unable to control the intracellular growth of Listeria monocytogenes (cytosolic infection), even though its cellular concentration largely exceeded the MIC (0.02 mg/liter) and minimal bactericidal concentration (2 mg/liter). We conclude that oritavancin enters cells by adsorptive endocytosis (favored by its lipophilic side chain and/or the presence of three protonatable amines), which drives it to lysosomes, where it exerts antibiotic activity.
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