New insights into the pharmacokinetics of vancomycin after oral and intravenous administration: an investigation in beagle dogs

Intestinal absorption of orally administered peptides is often negligible because one or more key requirements for successful absorption (water solubility, peptic resistance, mucosal permeation) are not met. Due to its high water solubility and stability in the gastro-intestinal tract, vancomycin is...

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Main Authors: Sauter, Max (Author) , Uhl, Philipp (Author) , Meid, Andreas (Author) , Mikus, Gerd (Author) , Burhenne, Jürgen (Author) , Haefeli, Walter E. (Author)
Format: Article (Journal)
Language:English
Published: 20 March 2020
In: Journal of pharmaceutical sciences
Year: 2020, Volume: 109, Issue: 6, Pages: 2090-2094
ISSN:1520-6017
DOI:10.1016/j.xphs.2020.03.012
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.xphs.2020.03.012
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0022354920301386
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Author Notes:Max Sauter, Philipp Uhl, Andreas D. Meid, Gerd Mikus, Jürgen Burhenne, Walter E. Haefeli
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Summary:Intestinal absorption of orally administered peptides is often negligible because one or more key requirements for successful absorption (water solubility, peptic resistance, mucosal permeation) are not met. Due to its high water solubility and stability in the gastro-intestinal tract, vancomycin is an ideal model peptide for evaluating the factors influencing the critical step of mucosal permeation. Therefore, to support formulation development for the systemic oral delivery of peptide therapeutics, we investigated the pharmacokinetics of vancomycin in beagle dogs after intravenous and oral administration comparing enteric encapsulated drug to the drug in solution, which revealed mean absolute bioavailabilities of 0.27% and 1.66%, respectively. Additionally, in depth pharmacokinetic analyses of intravenously administered vancomycin revealed a deep compartment slowly releasing the compound over many hours into the blood.
Item Description:Gesehen am 19.03.2021
Physical Description:Online Resource
ISSN:1520-6017
DOI:10.1016/j.xphs.2020.03.012