Teicoplanin metabolism in humans

Abstract

Teicoplanin, a lipoglycopeptide antibiotic, consists of five major components (A2-1 through A2-5), one hydrolysis component (A3-1), and four minor components (RS-1 through RS-4). All the major components contain an N-acyl-1-D-glucosamine, but they differ in the lengths and branchings of their acyl-aliphatic chains.Previous studies with radiolabeled teicoplanin in rats and humans have shown that the drug is eliminated by the renal route and that metabolic transformation is very minor, about 5%. A possible metabolic transformation of teicoplanin into A3-1 was also suggested. In the present study in humans, two metabolites (metabolites 1 and 2; 2 to 3% of total teicoplanin) were isolated after intravenous administration of radiolabeled teicoplanin. After purification, their structures were determined by fast atom bombardment mass spectroscopy and 'H nuclear magnetic resonance spectroscopy on the basis of the well-known correlations established in this field, and they were found to be new teicoplaninlike molecules, bearing 8-hydroxydecanoic and 9-hydroxydecanoic acyl moieties. This metabolic transformation is likely due to hydroxylation in the Q-2 and Q-1 positions for metabolites 1 and 2, respectively, of the C-10 linear side chain of component A2-3. This might explain the low extent of metabolism of teicoplanin if we consider that only component A2-3 has a linear chain that is susceptible to such oxidation.Teicoplanin (9) is a glycopeptide antibiotic that consists of a mixture of five major components designated A2-1, A2-2, A2-3, A2-4, and A2-5 and one more polar component designated A3-1 (5); minor components are also present (4, 8). All teicoplanin components are glycopeptide analogs with molecular weights that range from 1564.3 to 1907.7. The A3-1 component is the core glycopeptide that is common to all teicoplanin components that have been identified; it has a linear heptapeptide aglycone, an a-D-mannose, and an acetyl-o-D-glucosamine. All the components of the A2 group contain an additional N-acyl-p-D-glucosamine and differ only in the nature of this acyl-aliphatic chain (1, 4, 8) (Fig. 1). Teicoplanin components can be separated by gradient reversed-phase high-pressure liquid chromatography (HPLC) (Fig. 2) (13), by which it has been found that the A3-1 component is more polar than the A2 group components.Recovery studies with radiolabeled teicoplanin in rats (2, 16) and humans (7) following intravenous (i.v.) administration showed that the antibiotic is eliminated mainly by the renal route. In rats, approximately 70% of the administered dose is eliminated in 24 h, and 76% is eliminated in 120 h (2). In humans, elimination is slower; approximately 50% of the administered dose is recovered in the urine collected over 0 to 48 h after drug administration and 80% is recovered by 16 days (7). A study in rats with i.v. administration of teicoplanin showed little metabolic transformation of the antibiotic; in urine collected over 0 to 24 h after drug administration, no more than 3 to 5% of the dose eliminated was fo...

Population Pharmacokinetics of Teicoplanin in Children

“…The first relates to the composition and synthesis of the compound, which is a mixture of six related subcomponents (A2-1, A2-2, A2-3, A2-4, A2-5, and A3-1). The A3-1 component is the core glycopeptide that is common to all teicoplanin-like compounds (27). Concern has been expressed related to the composition of generic teicoplanin products and its potential impact on pharmacodynamics.…”

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Untitled

“…Its mechanism of action is to inhibit bacterial cell wall synthesis 2 . It works by stopping the bacteria making their cell walls and by disrupting their cell membranes 3 . Together, the cell wall and membrane form a barrier between the bacterial cell contents and the external environment.…”