Population Pharmacokinetic Modeling and Probability of Target Attainment of Ceftaroline in Brain and Soft Tissues
| Autor: | Victória Etges Helfer, Alexandre Prehn Zavascki, Markus Zeitlinger, Bibiana Verlindo de Araújo, Teresa Dalla Costa |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Antimicrob Agents Chemother |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | Ceftaroline, approved to treat skin infections and pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA), has been considered for the treatment of central nervous system (CNS) infections. A population pharmacokinetic (popPK) model was developed to describe ceftaroline soft tissue and cerebrospinal fluid (CSF) distributions and investigate the probability of target attainment (PTA) of the percentage of the dosing interval that the unbound drug concentration exceeded the MIC (%fT(>MIC)) to treat MRSA infections. Healthy subjects’ plasma and microdialysate concentrations from muscle and subcutaneous tissue following 600 mg every 12 h (q12h) and q8h and neurosurgical patients’ plasma and CSF concentrations following single 600-mg dosing were used. Plasma concentrations were described by a two-compartment model, and tissue concentrations were incorporated as three independent compartments linked to the central compartment by bidirectional transport (clearance in [CL(in)] and CL(out)). Apparent volumes were fixed to physiological interstitial values. Healthy status and body weight were identified as covariates for the volume of the central compartment, and creatinine clearance was identified for clearance. The CSF glucose concentration (GLUC) was inversely correlated with CL(in,CSF). Simulations showed a PTA of >90% in plasma and soft tissues for both regimens assuming an MIC of 1 mg/L and a %fT(>MIC) of 28.8%. Using the same target, patients with inflamed meninges (0.5 |
| Databáze: | OpenAIRE |
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