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Clinical Pharmacokinetics of Daptomycin

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Abstract

Due to the low level of resistance observed with daptomycin, this antibiotic has an important place in the treatment of severe Gram-positive infections. It is the first-in-class of the group of calcium-dependent, membrane-binding lipopeptides, and is a cyclic peptide constituted of 13 amino acids and an n-decanoyl fatty acid chain. The antibacterial action of daptomycin requires its complexation with calcium. Daptomycin is not absorbed from the gastrointestinal tract and needs to be administered parenterally. The distribution of daptomycin is limited (volume of distribution of 0.1 L/kg in healthy volunteers) due to its negative charge at physiological pH and its high binding to plasma proteins (about 90%). Its elimination is mainly renal, with about 50% of the dose excreted unchanged in the urine, justifying dosage adjustment for patients with renal insufficiency. The pharmacokinetics of daptomycin are altered under certain pathophysiological conditions, resulting in high interindividual variability. As a result, therapeutic drug monitoring of daptomycin may be of interest for certain patients, such as intensive care unit patients, patients with renal or hepatic insufficiency, dialysis patients, obese patients, or children. A target for the ratio of the area under the curve to the minimum inhibitory concentration > 666 is usually recommended for clinical efficacy, whereas in order to limit the risk of undesirable muscular effects the residual concentration should not exceed 24.3 mg/L.

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Fig. 1

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Authors and Affiliations

  1. INSERM, U1070, UFR de Médecine Pharmacie, Université de Poitiers, 1 rue Georges Bonnet, TSA 51106, 86073, Poitiers Cedex 9, France

    Nicolas Gregoire, Alexia Chauzy, Julien Buyck, Blandine Rammaert, William Couet & Sandrine Marchand

  2. Laboratoire de Toxicologie-Pharmacocinétique, CHU of Poitiers, 2 rue de la Miletrie, 86000, Poitiers, France

    Nicolas Gregoire, William Couet & Sandrine Marchand

  3. Service de maladies infectieuses et tropicales, CHU of Poitiers, 2 rue de la Miletrie, 86000, Poitiers, France

    Blandine Rammaert

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  1. Nicolas Gregoire
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  2. Alexia Chauzy
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Correspondence to William Couet.

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Nicolas Grégoire, Alexia Chauzy, Julien Buyck, Blandine Rammaert, Sandrine Marchand and William Couet declare they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Authors’ Contributions

NG carried out the bibliographical research, selection and evaluation of articles, their final selection, and the document writing AC carried out the bibliographical research, the selection and evaluation of articles and the writing of the document with special focus on pharmacokinetic. JB carried out the bibliographical research, the selection and evaluation of articles and the writing of the document with special focus on microbiology. BR carried out the bibliographical research, the selection and evaluation of articles and the writing of the document with special focus on clinical indications. SM carried out the revision of the document. WC carried out the final revision of the document.

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Gregoire, N., Chauzy, A., Buyck, J. et al. Clinical Pharmacokinetics of Daptomycin. Clin Pharmacokinet 60, 271–281 (2021). https://doi.org/10.1007/s40262-020-00968-x

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