Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update

Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update

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Daptomycin pharmacokinetics may not depend on renal function only and it significantly differs between healthy volunteers and severely ill patients.Herein, we propose a population pharmacokinetics model based on 424 plasma daptomycin concentrations collected from 156 patients affected by severe Gram-positive infections during a routine therapeutic drug monitoring protocol.Model building and validation were performed using NONMEM 7.2 (ICON plc), Xpose4 and Perl-speaks-to-NONMEM.

The final pop-PK model was a one-compartment first-order elimination model, with a 2.7% IIV for drug clearance (Cl), influence bostik universal primer pro of creatinine clearance on drug clearance and of sex on distribution volume.After model validation, we simulated 10,000 patients with the Monte-Carlo method to predict the efficacy and tolerability of different daptomycin daily dosages.For the most common 6 mg/kg daily dose, the simulated probability of overcoming the toxic minimum concentration (24.

3 mg/L) was 14.8% and the efficacy (expressed as a cumulative fraction of response) against methicillin-resistant S.aureus, S.pneumoniae 15-1 shampoo and E.

faecium was 95.77%, 99.99% and 68%, respectively.According to the model-informed precision dosing paradigm, pharmacokinetic models such as ours could help clinicians to perform patient-tailored antimicrobial dosing and maximize the odds of therapy success without neglecting toxicity risks.