Population pharmacokinetics of daptomycin in critically ill patients with various degrees of renal impairment

Grégoire, Nicolas; Marchand, Sandrine; Ferrandière, Martine; Lasocki, Sigismond; Séguin, Philippe; Vourc’h, Mickaël; Barbaz, Mathilde; Gaillard, Thomas; Launey, Yoann; Asehnoune, Karim; Couet, William; Mimoz, Olivier

doi:10.1093/jac/dky374

Cited by 19 publications

(22 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the PBPK models of the healthy population, we set the tissues type as permeability-limited because of the low volume of distribution of daptomycin. Then, we verified and optimized the models by comparing the predicted values with the observed values from the literature ( Dvorchik et al, 2003 ; Benvenuto et al, 2006 ; Abdel-Rahman et al, 2008 ; Cohen-Wolkowiez et al, 2012 ; Bradley et al, 2014 ; Gregoire et al, 2019 ). After optimization, the finalized healthy adults PBPK model served as the basis for developing the PBPK model of adults with renal impairment.…”

Section: Methodsmentioning

confidence: 99%

Physiologically based pharmacokinetic modeling of daptomycin dose optimization in pediatric patients with renal impairment

You

Zhou

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Background and Objective: Daptomycin is used to treat Gram-positive infections in adults and children and its dosing varies among different age groups. We focused on the pharmacokinetics of daptomycin in children with renal impairment, which has not been evaluated.Methods: A physiologically based pharmacokinetic (PBPK) model of daptomycin was established and validated to simulate its disposition in healthy populations and adults with renal impairment, along with a daptomycin exposure simulated in pediatric patients with renal impairment.Results: The simulated PBPK modeling results for various regimens of intravenously administered daptomycin were consistent with observed data according to the fold error below the threshold of 2. The Cmax and AUC of daptomycin did not differ significantly between children with mild-to-moderate renal impairment and healthy children. The AUC increased by an average of 1.55-fold and 1.85-fold in severe renal impairment and end-stage renal disease, respectively. The changes were more significant in younger children and could reach a more than 2-fold change. This scenario necessitates further daptomycin dose adjustments.Conclusion: Dose adjustments take into account the efficacy and safety of the drug; however, the steady-state Cmin of daptomycin may be above 24.3 mg/L in a few instances. We recommend monitoring creatine phosphokinase more than once a week when using daptomycin in children with renal impairment.

show abstract

Section: Methodsmentioning

confidence: 99%

Physiologically based pharmacokinetic modeling of daptomycin dose optimization in pediatric patients with renal impairment

You

Zhou

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Antibiotics are subject to changes in PK/PD parameters in sepsis and septic shock where resultant concentrations may be too low risking clinical failure, or too high leading to toxicity (Table 3) [237][238][239]. Augmented renal clearance [240], AKI [241], hypoalbuminemia [242], RRT [243,244], and extracorporeal membrane oxygenation [245,246] are examples of common scenarios that affect the concentrations of some antibiotics. Administration of antibiotics using an approach that adheres to PK/PD principles and using dosing regimens developed in patients with sepsis and septic shock is more likely to result in effective and safe drug concentrations compared to use of dosing recommendations provided in the manufacturer's product information [247].…”

Section: Rationalementioning

confidence: 99%

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021

et al. 2021

View full text Add to dashboard Cite

“…The latter methodology may seem more suitable for the determination of protein binding of drugs, such as PMB, that exhibit significant nonspecific binding to laboratory material including ultrafiltration membranes ( Cheah et al, 2015 ). Although, ultrafiltration has also been used to determine unbound concentrations of daptomycin, another antibiotic known to adhere to ultrafiltration membranes, after evaluation of non-specific binding by regression methods ( Kim et al, 2008 ; Grégoire et al, 2019 ). This two-fold difference in unbound fractions should complicate PKPD modeling comparisons between these two studies, but not the IE investigated during this new study.…”

Section: Discussionmentioning

confidence: 99%

PKPD Modeling of the Inoculum Effect of Acinetobacter baumannii on Polymyxin B in vivo

et al. 2022

Self Cite

View full text Add to dashboard Cite

The reduction in antimicrobial activity at high bacterial counts is a microbiological phenomenon known as the inoculum effect (IE). In a previous in vitro study, a significant IE was observed for polymyxin B (PMB) against a clinical isolate of Acinetobacter baumannii, and well described by a new pharmacokinetic-pharmacodynamic model. Few in vivo studies have investigated the impact of inoculum size on survival or antibiotic efficacy. Therefore, our objective was to confirm the influence of inoculum size of this A. baumannii clinical isolate on PMB in vivo effect over time. Pharmacokinetics and pharmacodynamics of PMB after a single subcutaneous administration (1, 15 and 40 mg/kg) were studied in a neutropenic murine thigh infection model. The impact of A. baumannii inoculum size (105, 106 and 107 CFU/thigh) on PMB efficacy was also evaluated. In vivo PMB PK was well described by a two-compartment model including saturable absorption from the subcutaneous injection site and linear elimination. The previous in vitro PD model was modified to adequately describe the decrease of PMB efficacy with increased inoculum size in infected mice. The IE was modeled as a decrease of 32% in the in vivo PMB bactericidal effect when the starting inoculum increases from 105 to 107 CFU/thigh. Although not as important as previously characterized in vitro an IE was confirmed in vivo.

show abstract

Population pharmacokinetics of daptomycin in critically ill patients with various degrees of renal impairment

Cited by 19 publications

References 29 publications

Physiologically based pharmacokinetic modeling of daptomycin dose optimization in pediatric patients with renal impairment

Physiologically based pharmacokinetic modeling of daptomycin dose optimization in pediatric patients with renal impairment

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021

PKPD Modeling of the Inoculum Effect of Acinetobacter baumannii on Polymyxin B in vivo

Contact Info

Product

Resources

About