Population Pharmacokinetic and Pharmacodynamic Analysis of Dalbavancin for Long-Term Treatment of Subacute and/or Chronic Infectious Diseases: The Major Role of Therapeutic Drug Monitoring

• Κύριοι συγγραφείς: Pier Giorgio Cojutti (Συγγραφέας), Sara Tedeschi (Συγγραφέας), Milo Gatti (Συγγραφέας), Eleonora Zamparini (Συγγραφέας), Marianna Meschiari (Συγγραφέας), Paola Della Siega (Συγγραφέας), Maria Mazzitelli (Συγγραφέας), Laura Soavi (Συγγραφέας), Raffaella Binazzi (Συγγραφέας), Elke Maria Erne (Συγγραφέας), Marco Rizzi (Συγγραφέας), Anna Maria Cattelan (Συγγραφέας), Carlo Tascini (Συγγραφέας), Cristina Mussini (Συγγραφέας), Pierluigi Viale (Συγγραφέας), Federico Pea (Συγγραφέας)
• Μορφή: Βιβλίο
• Έκδοση: MDPI AG, 2022-07-01T00:00:00Z.
• Θέματα: article
• Διαθέσιμο Online: Connect to this object online.
• Notes: 10.3390/antibiotics11080996; 2079-6382
• Keywords: dalbavancin; population pharmacokinetics; therapeutic drug monitoring; long-term treatment; off-label use; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 11, Iss 8, p 996 (2022)

A population pharmacokinetic analysis of dalbavancin was conducted in patients with different infection sites. Non-linear mixed effect modeling was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations assessed the probability of target attainment (PTA) of total dalbavancin concentration ≥ 8.04 mg/L over time (associated with ≥90% probability of optimal pharmacodynamic target attainment of <i>f</i>AUC_24h/MIC > 111.1 against <i>S. aureus</i>) associated with a single or double dosage, one week apart, of 1000 or 1500 mg in patients with different classes of renal function. Sixty-nine patients with 289 concentrations were included. Most of them (53/69, 76.8%) had bone and joint infections. A two-compartment model adequately fitted dalbavancin concentration-time data. Creatinine clearance (CL_CR) was the only covariate associated with dalbavancin clearance. Monte Carlo simulations showed that, in patients with severe renal dysfunction, the 1000 mg single or double one week apart dosage may ensure optimal PTAs of 2 and 5 weeks, respectively. In patients with preserved renal function, the 1500 mg single or double one-week apart dosage may ensure optimal PTAs of 2 and 4 to 6 weeks, respectively. Therapeutic drug monitoring should be considered mandatory for managing inter-individual variability and for supporting clinicians in long-term treatments of subacute and chronic infections.