Characterization of the Interaction of Daptomycin With Site II on Human Serum Albumin.

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Yamasaki K, Sakurama K, Nishi K, Watanabe H, Maruyama T, Seo H, Otagiri M, Taguchi K

Characterization of the Interaction of Daptomycin With Site II on Human Serum Albumin.

J Pharm Sci. 2020 Sep;109(9):2919-2924. doi: 10.1016/j.xphs.2020.06.011. Epub 2020 Jun 18.

PubMed ID

32565355 [ View in PubMed

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Abstract

Daptomycin, a cyclic lipopeptide antibiotic, is clinically used for the treatment of infections caused by Gram-positive bacteria, including the methicillin-resistant Staphylococcus aureus and the vancomycin-resistant Enterococci. While daptomycin shows high plasma protein binding (90-93%), our knowledge of the binding process is not extensive. To address this issue in more detail, we characterized the binding of daptomycin to plasma proteins and the findings indicate that the association constant for the binding of daptomycin to human serum albumin (HSA) is much higher than that for alpha1-acid glycoprotein, another plasma protein. Daptomycin was also found to bind to a single site on HSA, which was identified as site II. The findings also suggest that the n-decanoyl moiety of daptomycin penetrates into the hydrophobic pocket of site II and that this acyl moiety interacts with Tyr411 at the entrance to site II. Due to this selective interaction with site II, daptomycin binding was significantly inhibited by drugs (ibuprofen or diazepam) and endogenous compounds (uremic toxins or fatty acids) which also strongly bind to site II. In diseased states, such an inhibition in the binding could result in the pharmacokinetics and therapeutic action of daptomycin being substantially altered.

DrugBank Data that Cites this Article

Drugs

Daptomycin

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Daptomycin	Alpha-1-acid glycoprotein 1	Protein	Humans	No	Binder	Details
Daptomycin	Serum albumin	Protein	Humans	No	Binder	Details