1. Clinical Pharmacokinetics of Daptomycin
- Author
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William Couet, Sandrine Marchand, Blandine Rammaert, Julien M. Buyck, Nicolas Grégoire, Alexia Chauzy, Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, and Chauzy, Alexia
- Subjects
0301 basic medicine ,medicine.drug_class ,[SDV]Life Sciences [q-bio] ,030106 microbiology ,Antibiotics ,Microbial Sensitivity Tests ,Pharmacology ,03 medical and health sciences ,Minimum inhibitory concentration ,0302 clinical medicine ,Pharmacokinetics ,Daptomycin ,medicine ,Distribution (pharmacology) ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Volume of distribution ,medicine.diagnostic_test ,business.industry ,Area under the curve ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,3. Good health ,Anti-Bacterial Agents ,[SDV] Life Sciences [q-bio] ,[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences ,Therapeutic drug monitoring ,Area Under Curve ,Drug Monitoring ,business ,medicine.drug - Abstract
International audience; 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.
- Published
- 2020
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