Population pharmacokinetics and dosing considerations for the use of daptomycin in adult patients with haematological malignancies



Cojutti, Pier Giorgio, Candoni, Anna, Ramos-Martin, Virginia, lazzarotto, DaviDe, Zannier, Maria Elena, Fanin, Renato, Hope, William ORCID: 0000-0001-6187-878X and Pea, Federico
(2017) Population pharmacokinetics and dosing considerations for the use of daptomycin in adult patients with haematological malignancies. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 72 (8). pp. 2342-2350.

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Abstract

<h4>Objectives</h4>To assess the population pharmacokinetics (popPK) of daptomycin at the conventional dose of 6 mg/kg/day in a cohort of oncohaematological patients.<h4>Methods</h4>Patients underwent serial blood sampling on day 3 of therapy (before dosing and at 0, 0.5, 1, 2, 3, 5, 7, 9 and 12 h after dosing) to assess the pharmacokinetic profile of daptomycin. PopPK and Monte Carlo simulation were performed to define the probability of target attainment (PTA) with 6, 8, 10 and 12 mg/kg/day of the pharmacokinetic/pharmacodynamic target of AUC 24 /MIC >1081.<h4>Results</h4>Thirty patients were recruited. A two-compartment open model with first-order intravenous input and first-order elimination was developed. Estimated creatinine clearance (CL CR ), serum albumin concentration (Alb) and presence of AML were covariates included in the final model. Monte Carlo simulation showed that the conventional 6 mg/kg/day dose resulted in optimal PTAs (≥80%) in the presence of pathogens with an MIC up to 0.5 mg/L only in patients with CL CR 50-100 mL/min/1.73 m 2 , Alb 26-45 g/L and a haematological diagnosis other than AML. Conversely, higher dosages, up to 12 mg/kg/day, were needed to achieve this goal in the presence of pathogens with an MIC of 0.25-0.5 mg/L in all of the other tested scenarios. In patients with CL CR 101-150 mL/min/1.73 m 2 and Alb 15-25 g/L, suboptimal PTAs (<60%) were predicted even with 12 mg/kg/day dosing .<h4>Conclusions</h4>Our study provides a strong rationale for considering daptomycin dosages of ≥ 8 mg/kg/day in several clinical scenarios for oncohaematological patients. In some of these scenarios therapeutic drug monitoring could be a useful adjunct for optimized care.

Item Type: Article
Uncontrolled Keywords: Plasma, Humans, Bacterial Infections, Hematologic Neoplasms, Daptomycin, Anti-Bacterial Agents, Microbial Sensitivity Tests, Monte Carlo Method, Prospective Studies, Adult, Middle Aged, Female, Male
Depositing User: Symplectic Admin
Date Deposited: 14 Jul 2017 13:39
Last Modified: 19 Jan 2023 06:59
DOI: 10.1093/jac/dkx140
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3008485