Evaluation of pharmacokinetics and the stability of daptomycin in serum at various temperatures

Ogami, Chika; Tsuji, Yasuhiro; Kasai, Hidefumi; Hiraki, Yoichi; Yamamoto, Yoshihiro; Matsunaga, Kazuhisa; Karube, Yoshiharu; To, Hideto

doi:10.1016/j.ijid.2017.01.017

Cited by 13 publications

(4 citation statements)

References 25 publications

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“…Five serial blood samples were collected from a peripheral vein from day 4 (steady state) at the pre-dose, 0.5, 1–2, 4–10 h after the infusion ended and before the next dose. According to a TDM protocol for daptomycin adopted in these hospitals, the samples, collected in an additive-free tube, were centrifuged and the serum was stored at −20 °C until the drug concentrations were measured [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Population Pharmacokinetic/Pharmacodynamic Modelling of Daptomycin for Schedule Optimization in Patients with Renal Impairment

García‐Martínez

Bellés-Medall²,

Garcia‐Cremades

et al. 2022

Pharmaceutics

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The aims of this study are (i) to develop a population pharmacokinetic/pharmacodynamic model of daptomycin in patients with normal and impaired renal function, and (ii) to establish the optimal dose recommendation of daptomycin in clinical practice. Several structural PK models including linear and non-linear binding kinetics were evaluated. Monte Carlo simulations were conducted with a fixed combination of creatinine clearance (30–90 mL/min/1.73 m2) and body weight (50–100 kg). The final dataset included 46 patients and 157 daptomycin observations. A two-compartment model with first-order peripheral distribution and elimination kinetics assuming non-linear protein-binding kinetics was selected. The bactericidal effect for Gram+ strains with MIC ≤ 0.5 mg/L could be achieved with 5–12 mg/kg daily daptomycin based on body weight and renal function. The administration of 10–17 mg/kg q48 h daptomycin allows to achieve bactericidal effect for Gram+ strains with MIC ≤ 1 mg/L. Four PK samples were selected as the optimal sampling strategy for an accurate AUC estimation. A quantitative framework has served to characterize the non-linear binding kinetics of daptomycin in patients with normal and impaired renal function. The impact of different dosing regimens on the efficacy and safety outcomes of daptomycin treatment based on the unbound exposure of daptomycin and individual patient characteristics has been evaluated.

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Section: Methodsmentioning

confidence: 99%

Population Pharmacokinetic/Pharmacodynamic Modelling of Daptomycin for Schedule Optimization in Patients with Renal Impairment

García‐Martínez

Bellés-Medall²,

Garcia‐Cremades

et al. 2022

Pharmaceutics

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“…The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/antibiotics12050904/s1, supplemental information S1: Supplemental informations: material and methods [64]; Table S1: Additional informations. Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.…”

Section: Supplementary Materialsmentioning

confidence: 99%

Daptomycin Pharmacokinetics in Blood and Wound Fluid in Critical Ill Patients with Left Ventricle Assist Devices

Calov

Münzel²,

Roehr³

et al. 2023

Antibiotics

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Daptomycin is a cyclic lipopeptide antibiotic with bactericidal effects against multidrug-resistant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). For critically ill patients, especially in the presence of implants, daptomycin is an important therapeutic option. Left ventricle assist devices (LVADs) can be utilized for intensive care patients with end-stage heart failure as a bridge to transplant. We conducted a single-center prospective trial with critically ill adults with LVAD who received prophylactic anti-infective therapy with daptomycin. Our study aimed to evaluate the pharmacokinetics of daptomycin in the blood serum and wound fluids after LVAD implantation. Daptomycin concentration were assessed over three days using high-performance liquid chromatography (HPLC). We detected a high correlation between blood serum and wound fluid daptomycin concentration at 12 h (IC95%: 0.64 to 0.95; r = 0.86; p < 0.001) and 24 h (IC95%: −0.38 to 0.92; r = 0.76; p < 0.001) after antibiotic administration. Our pilot clinical study provides new insights into the pharmacokinetics of daptomycin from the blood into wound fluids of critically ill patients with LVADs.

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“…DAP is hydrolyzed and inactivated by general proteases, which indicates that hydrolysis by proteases in the human body or serum may influence the PK of DAP and its stability in the corrected serum samples of patients. 48) The activities of proteases generally vary with temperature. Therefore, we evaluated the stability of DAP in serum at various temperatures by repeatedly measuring DAP concentration.…”

Section: Pharmacokinetics Of Daptomycinmentioning

confidence: 99%

Hospital Pharmacometrics for Optimal Individual Administration of Antimicrobial Agents for Anti-methicillin-resistant <i>Staphylococcus aureus</i> Infected Patients

Tsuji

2021

Biological & Pharmaceutical Bulletin

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Therapeutic drug monitoring and target concentration intervention based on population pharmacokinetic and pharmacodynamic models has been strongly recommended for anti-methicillin-resistant Staphylococcus aureus (MRSA) agents in order to provide appropriate antimicrobial chemotherapy to each individual patient, and pharmacokinetic and pharmacodynamic analyses in hospitalized patients have been actively conducted, as evidenced with vancomycin. Teicoplanin, daptomycin, and linezolid have been the most studied antibiotics, using population pharmacokinetics of patients with MRSA. Infections caused by MRSA have higher severity and fatality rates than other antimicrobial-susceptible infections. Therefore, many medical facilities have been implementing infection control programs based on antimicrobial stewardship to prevent nosocomial infections and drug-resistant strains. Studies detailing pharmacometrics for these antibiotics have been reported to elucidate the pharmacokinetic and pharmacodynamic properties, to determine significant factors influencing variabilities between individuals, and to develop target concentration interventions and dosing regimens for adults, the elderly, patients with renal insufficiency including those on continuous renal replacement therapies, patients with low body weight, obese patients, and pediatric patients. This review presents the details of our recent research on the optimal dosing design of antimicrobial agents for the treatment of MRSA infection based on hospital pharmacometrics. In addition, the prospect of using modeling and simulation has shown major advantages in supporting dosing regimen selection.

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Evaluation of pharmacokinetics and the stability of daptomycin in serum at various temperatures

Abstract: The results of the present study demonstrate that the measurement of serum concentrations of daptomycin needs to be performed rapidly. Furthermore, the degradation of daptomycin in serum may be involved in its elimination from the living body.

Cited by 13 publications

References 25 publications

Population Pharmacokinetic/Pharmacodynamic Modelling of Daptomycin for Schedule Optimization in Patients with Renal Impairment

Population Pharmacokinetic/Pharmacodynamic Modelling of Daptomycin for Schedule Optimization in Patients with Renal Impairment

Daptomycin Pharmacokinetics in Blood and Wound Fluid in Critical Ill Patients with Left Ventricle Assist Devices

Hospital Pharmacometrics for Optimal Individual Administration of Antimicrobial Agents for Anti-methicillin-resistant <i>Staphylococcus aureus</i> Infected Patients

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