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 grandpas best 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 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 macallan hip flask efficacy (expressed as a cumulative fraction of response) against methicillin-resistant S.aureus, S.pneumoniae 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.