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Teicoplanin metabolism in humans
A Bernareggi1, A Borghi, M Borgonovi
1Lepetit Research Center, Marion Merrell Dow Research Institute, Gerenzano (VA), Italy.
Antimicrobial Agents and Chemotherapy
|August 1, 1992
Summary
Teicoplanin metabolism in humans is minimal, with two new hydroxylated metabolites identified. These teicoplanin-like molecules result from oxidation of the A2-3 component, explaining its low metabolic transformation.
Area of Science:
- Pharmacology
- Medicinal Chemistry
- Analytical Chemistry
Background:
- Teicoplanin is a lipoglycopeptide antibiotic with multiple components.
- Previous studies indicated minimal metabolism (around 5%) and renal excretion of teicoplanin.
- A potential metabolic transformation into A3-1 was previously suggested.
Purpose of the Study:
- To identify and characterize teicoplanin metabolites in humans.
- To elucidate the metabolic pathways of teicoplanin.
- To explain the low extent of teicoplanin metabolism.
Main Methods:
- Intravenous administration of radiolabeled teicoplanin to human subjects.
- Isolation and purification of metabolites.
- Structural elucidation using fast atom bombardment mass spectroscopy and 1H nuclear magnetic resonance spectroscopy.
Main Results:
- Two new teicoplanin metabolites (metabolites 1 and 2) were isolated, representing 2-3% of the total administered dose.
- The metabolites were identified as teicoplanin-like molecules with 8-hydroxydecanoic and 9-hydroxydecanoic acyl moieties.
- Metabolic transformation likely involves hydroxylation of the linear side chain of teicoplanin component A2-3 at the omega-2 and omega-1 positions.
Conclusions:
- Teicoplanin undergoes very minor metabolic transformation in humans, primarily through hydroxylation of the A2-3 component.
- The identified metabolites are novel teicoplanin-like molecules.
- The susceptibility of the A2-3 component's linear side chain to oxidation explains the low overall metabolism of teicoplanin.