Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update
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 Gra...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/7/914 |
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| author | Giuseppe Balice Claudio Passino Maria Grazia Bongiorni Luca Segreti Alessandro Russo Marianna Lastella Giacomo Luci Marco Falcone Antonello Di Paolo |
| author_facet | Giuseppe Balice Claudio Passino Maria Grazia Bongiorni Luca Segreti Alessandro Russo Marianna Lastella Giacomo Luci Marco Falcone Antonello Di Paolo |
| author_sort | Giuseppe Balice |
| collection | DOAJ |
| description | 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 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 <i>S. aureus</i>, <i>S. pneumoniae</i> and <i>E. faecium</i> 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. |
| first_indexed | 2024-03-09T12:20:38Z |
| format | Article |
| id | doaj.art-316bbd8236764523a3e3c52d9c61f0d1 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T12:20:38Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-316bbd8236764523a3e3c52d9c61f0d12023-11-30T22:41:18ZengMDPI AGAntibiotics2079-63822022-07-0111791410.3390/antibiotics11070914Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An UpdateGiuseppe Balice0Claudio Passino1Maria Grazia Bongiorni2Luca Segreti3Alessandro Russo4Marianna Lastella5Giacomo Luci6Marco Falcone7Antonello Di Paolo8Sant’Anna School of Advanced Studies, Piazza Martiri della Libertà, 56127 Pisa, ItalySant’Anna School of Advanced Studies, Piazza Martiri della Libertà, 56127 Pisa, ItalyUnit of Cardiovascular Diseases, Pisa University Hospital, Via Paradisa 2, 56100 Pisa, ItalyUnit of Cardiovascular Diseases, Pisa University Hospital, Via Paradisa 2, 56100 Pisa, ItalyInfectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, “Magna Graecia” University of Catanzaro, Viale Europa, 88100 Catanzaro, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, ItalyUnit of Infectious Diseases, Pisa University Hospital, Via Paradisa 2, 56100 Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, ItalyDaptomycin 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 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 <i>S. aureus</i>, <i>S. pneumoniae</i> and <i>E. faecium</i> 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.https://www.mdpi.com/2079-6382/11/7/914daptomycinpopulation pharmacokineticssimulationefficacytoxicity |
| spellingShingle | Giuseppe Balice Claudio Passino Maria Grazia Bongiorni Luca Segreti Alessandro Russo Marianna Lastella Giacomo Luci Marco Falcone Antonello Di Paolo Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update Antibiotics daptomycin population pharmacokinetics simulation efficacy toxicity |
| title | Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update |
| title_full | Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update |
| title_fullStr | Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update |
| title_full_unstemmed | Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update |
| title_short | Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update |
| title_sort | daptomycin population pharmacokinetics in patients affected by severe gram positive infections an update |
| topic | daptomycin population pharmacokinetics simulation efficacy toxicity |
| url | https://www.mdpi.com/2079-6382/11/7/914 |
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