Multidose Dalbavancin Population Pharmacokinetic Analysis for Prolonged Target Attainment in Patients Requiring Long-Term Treatment
<b>Introduction:</b> Dalbavancin (DAL) is a long-acting lipoglycopeptide active against Gram-positive bacteria, including multidrug-resistant isolates. A growing body of evidence supports its efficacy in various difficult-to-treat infections. DAL shows time-dependent bactericidal activit...
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MDPI AG
2025-02-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/14/2/190 |
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| author | Giammarco Baiardi Michela Cameran Caviglia Silvia Boni Antonello Di Paolo Valeria Marini Giuliana Cangemi Alessia Cafaro Emanuele Pontali Francesca Mattioli |
| author_facet | Giammarco Baiardi Michela Cameran Caviglia Silvia Boni Antonello Di Paolo Valeria Marini Giuliana Cangemi Alessia Cafaro Emanuele Pontali Francesca Mattioli |
| author_sort | Giammarco Baiardi |
| collection | DOAJ |
| description | <b>Introduction:</b> Dalbavancin (DAL) is a long-acting lipoglycopeptide active against Gram-positive bacteria, including multidrug-resistant isolates. A growing body of evidence supports its efficacy in various difficult-to-treat infections. DAL shows time-dependent bactericidal activity <i>in vitro</i> at free drug concentrations equal to 4×MIC values. However, the optimal dosing scheme for achieving the PK/PD target in multidose treatment has not been fully established. <b>Methods:</b> Pharmacokinetic analysis was based on a nonlinear mixed effects modelling approach performed in NONMEM v7.5/Pirana, while R was used for data management and graphical summaries. Final model parameters were used to simulate the plasma disposition of DAL by Monte Carlo simulations to determine the multidose DAL regimen associated with a 90% target attainment of 100% <i>f</i>T > 4×MIC. <b>Results:</b> A two-compartmental model with first-order elimination and allometric-scaled bodyweight best described DAL disposition in patients with CLcr > 30 mL/min. Monte Carlo simulations showed that two 1500 mg DAL doses 7 days apart granted an optimal PTA > 90% of 100% <i>f</i>T > 4×MIC up to 5, 4, and 3 weeks in patients weighting from 40–80 kg, 80–120 kg and 120–200 kg, respectively. An additional third 1500 mg dose at the above time points by weight bands may extend the optimal PTA up to 9, 7, and 6 weeks of total treatment. <b>Conclusions:</b> Two 1500 mg DAL doses administered 7 days apart could be a valuable starting strategy for patients of all weight classes with CLcr > 30 mL/min. In patients requiring long-term DAL treatment, the optimal timing of additional administrations should be guided by routine TDM or empirically through patients’ total body weight when TDM is unavailable. |
| format | Article |
| id | doaj-art-6bc5cf26d6fe44fcbab3b487fad7c39e |
| institution | DOAJ |
| issn | 2079-6382 |
| language | English |
| publishDate | 2025-02-01 |
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| series | Antibiotics |
| spelling | doaj-art-6bc5cf26d6fe44fcbab3b487fad7c39e2025-08-20T03:11:06ZengMDPI AGAntibiotics2079-63822025-02-0114219010.3390/antibiotics14020190Multidose Dalbavancin Population Pharmacokinetic Analysis for Prolonged Target Attainment in Patients Requiring Long-Term TreatmentGiammarco Baiardi0Michela Cameran Caviglia1Silvia Boni2Antonello Di Paolo3Valeria Marini4Giuliana Cangemi5Alessia Cafaro6Emanuele Pontali7Francesca Mattioli8Pharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa, ItalyPharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa, ItalyDepartment of Infectious Diseases, Ente Ospedaliero Ospedali Galliera, 16128 Genoa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, ItalyPharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa, ItalyBiochemistry, Pharmacology and Newborn Screening Unit, Central Laboratory of Analysis, IRCCS Istituto Giannina, Gaslini, 16147 Genova, ItalyBiochemistry, Pharmacology and Newborn Screening Unit, Central Laboratory of Analysis, IRCCS Istituto Giannina, Gaslini, 16147 Genova, ItalyDepartment of Infectious Diseases, Ente Ospedaliero Ospedali Galliera, 16128 Genoa, ItalyPharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy<b>Introduction:</b> Dalbavancin (DAL) is a long-acting lipoglycopeptide active against Gram-positive bacteria, including multidrug-resistant isolates. A growing body of evidence supports its efficacy in various difficult-to-treat infections. DAL shows time-dependent bactericidal activity <i>in vitro</i> at free drug concentrations equal to 4×MIC values. However, the optimal dosing scheme for achieving the PK/PD target in multidose treatment has not been fully established. <b>Methods:</b> Pharmacokinetic analysis was based on a nonlinear mixed effects modelling approach performed in NONMEM v7.5/Pirana, while R was used for data management and graphical summaries. Final model parameters were used to simulate the plasma disposition of DAL by Monte Carlo simulations to determine the multidose DAL regimen associated with a 90% target attainment of 100% <i>f</i>T > 4×MIC. <b>Results:</b> A two-compartmental model with first-order elimination and allometric-scaled bodyweight best described DAL disposition in patients with CLcr > 30 mL/min. Monte Carlo simulations showed that two 1500 mg DAL doses 7 days apart granted an optimal PTA > 90% of 100% <i>f</i>T > 4×MIC up to 5, 4, and 3 weeks in patients weighting from 40–80 kg, 80–120 kg and 120–200 kg, respectively. An additional third 1500 mg dose at the above time points by weight bands may extend the optimal PTA up to 9, 7, and 6 weeks of total treatment. <b>Conclusions:</b> Two 1500 mg DAL doses administered 7 days apart could be a valuable starting strategy for patients of all weight classes with CLcr > 30 mL/min. In patients requiring long-term DAL treatment, the optimal timing of additional administrations should be guided by routine TDM or empirically through patients’ total body weight when TDM is unavailable.https://www.mdpi.com/2079-6382/14/2/190dalbavancindrug monitoringpopulation pharmacokineticsPK/PD targetpersonalized medicine |
| spellingShingle | Giammarco Baiardi Michela Cameran Caviglia Silvia Boni Antonello Di Paolo Valeria Marini Giuliana Cangemi Alessia Cafaro Emanuele Pontali Francesca Mattioli Multidose Dalbavancin Population Pharmacokinetic Analysis for Prolonged Target Attainment in Patients Requiring Long-Term Treatment Antibiotics dalbavancin drug monitoring population pharmacokinetics PK/PD target personalized medicine |
| title | Multidose Dalbavancin Population Pharmacokinetic Analysis for Prolonged Target Attainment in Patients Requiring Long-Term Treatment |
| title_full | Multidose Dalbavancin Population Pharmacokinetic Analysis for Prolonged Target Attainment in Patients Requiring Long-Term Treatment |
| title_fullStr | Multidose Dalbavancin Population Pharmacokinetic Analysis for Prolonged Target Attainment in Patients Requiring Long-Term Treatment |
| title_full_unstemmed | Multidose Dalbavancin Population Pharmacokinetic Analysis for Prolonged Target Attainment in Patients Requiring Long-Term Treatment |
| title_short | Multidose Dalbavancin Population Pharmacokinetic Analysis for Prolonged Target Attainment in Patients Requiring Long-Term Treatment |
| title_sort | multidose dalbavancin population pharmacokinetic analysis for prolonged target attainment in patients requiring long term treatment |
| topic | dalbavancin drug monitoring population pharmacokinetics PK/PD target personalized medicine |
| url | https://www.mdpi.com/2079-6382/14/2/190 |
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