In silico molecular targets, docking, dynamics simulation and physiologically based pharmacokinetics modeling of oritavancin.
Antibiotic
Molecular dynamics simulation
Molecular target
Oritavancin
PBPK modeling
Pharmacokinetics
Journal
BMC pharmacology & toxicology
ISSN: 2050-6511
Titre abrégé: BMC Pharmacol Toxicol
Pays: England
ID NLM: 101590449
Informations de publication
Date de publication:
22 Oct 2024
22 Oct 2024
Historique:
received:
01
08
2024
accepted:
16
10
2024
medline:
23
10
2024
pubmed:
23
10
2024
entrez:
23
10
2024
Statut:
epublish
Résumé
Oritavancin is a semi-synthetic lipoglycopeptide antibiotic primarily used to treat serious infections caused by Gram-positive bacteria. The aim of this study was to elucidate possible molecular targets of oritavancin in human and microbes in relevance to its mechanism of action and model its pharmacokinetics for optimal dose selection in clinical practice. Computational methods were used in this study which include target prediction, molecular docking, molecular dynamics simulation, pharmacokinetics prediction, and physiological-based pharmacokinetics (PBPK) modeling. Oritavancin was moderately soluble in water and did not permeate the blood-brain barrier. Seven molecular targets were identified in humans. Molecular docking results showed highest binding affinity of oritavancin with PI3-kinase p110-gamma subunit (-10.34 kcal/mol), followed by Acyl-CoA desaturase (-10.07 kcal/mol) and Cytochrome P450 2C19 (-8.384 kcal/mol). Oritavancin PBPK modelling in adult human showed that infusion has lower peak concentrations (Cmax) compared to bolus administration, with 1200 mg dose yielded Cmax of 16.559 mg/L, 800 mg dose yielded Cmax of 11.258 mg/L, and 200 mg over 3 days dose yielded Cmax of 7.526 mg/L. Notably, infusion gave extended half-life (t This comprehensive computational study has provided invaluable insights into the pharmacological profile of Oritavancin, aiding its further development and optimization for clinical use.
Identifiants
pubmed: 39439008
doi: 10.1186/s40360-024-00804-z
pii: 10.1186/s40360-024-00804-z
doi:
Substances chimiques
oritavancin
PUG62FRZ2E
Lipoglycopeptides
0
Anti-Bacterial Agents
0
Glycopeptides
0
Vancomycin
6Q205EH1VU
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
79Informations de copyright
© 2024. The Author(s).
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