Pharmacokinetic/pharmacodynamic target attainment analyses to support intravenous and oral lefamulin dose selection for the treatment of patients with community-acquired bacterial pneumonia.
J Antimicrob Chemother
; 74(Suppl 3): iii35-iii41, 2019 04 01.
Article
en En
| MEDLINE
| ID: mdl-30949705
ABSTRACT
OBJECTIVES:
Lefamulin is a semi-synthetic intravenous (iv) and oral pleuromutilin antibiotic active against community-acquired bacterial pneumonia (CABP) pathogens. Pharmacokinetic/pharmacodynamic (PK/PD) target attainment analyses were carried out to evaluate lefamulin 150 mg iv q12h and 600 mg orally q12h under fed and fasted conditions for the treatment of patients with CABP.METHODS:
The analyses undertaken used a population PK model based on Phase 1 PK data, non-clinical PK/PD targets for efficacy and in vitro surveillance data for Streptococcus pneumoniae (SP) and Staphylococcus aureus (SA), and Monte Carlo simulation. Percentage probabilities of PK/PD target attainment by MIC on day 1 were determined using median total-drug epithelial lining fluid (ELF) and free-drug plasma AUCMIC ratio targets associated with 1 and 2 log10 cfu reductions from baseline.RESULTS:
Percentage probabilities of attaining the total-drug ELF AUCMIC ratio target for a 1 log10 cfu reduction from baseline for SP were ≥99.2% at the MIC90 of 0.12 mg/L and 96.7%, 82.1% and 96.3% for iv and oral dosing regimens under fed and fasted conditions, respectively, at the MIC99 of 0.25 mg/L. Percentage probabilities of attaining the free-drug plasma AUCMIC target for the same endpoint at the SP MIC99 were 100% for each regimen. For the SA MIC90 of 0.12 mg/L and AUCMIC ratio targets for the same endpoint, percentage probabilities were 92.7%-100% for iv and oral dosing regimens.CONCLUSIONS:
These data provide support for lefamulin 150 mg iv q12h and 600 mg orally q12h for the treatment of patients with CABP and suggest that doses may not need to be taken under fasted conditions.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Compuestos Policíclicos
/
Tioglicolatos
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Bacterias
/
Simulación por Computador
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Infecciones Comunitarias Adquiridas
/
Diterpenos
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Antibacterianos
Tipo de estudio:
Health_economic_evaluation
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos