Pharmacokinetic/pharmacodynamic analysis of high-dose tigecycline, by Monte Carlo simulation, in plasma and sputum of patients with hospital-acquired pneumonia.
J Clin Pharm Ther
; 47(12): 2312-2319, 2022 Dec.
Article
em En
| MEDLINE
| ID: mdl-36479719
ABSTRACT
WHAT IS KNOWN AND OBJECTIVE:
To Investigate the pharmacokinetic/pharmacodynamic (PK/PD) parameters of high-dose tigecycline in plasma and sputum of patients with hospital-acquired pneumonia (HAP), and provide a therapeutic regimen of multidrug-resistant bacteria (MDRB) infections.METHODS:
Blood/sputum samples were collected at intervals after tigecycline had reached a steady-state. Tigecycline concentrations in specimens were determined by high-performance liquid chromatography (HLPC), PK parameters were evaluated by WinNonlin software using a non-compartment model. The probability of target attainments (PTAs) at different minimal inhibitory concentrations (MICs) were calculated for achieving the PK/PD index with Crystal Ball software by 10,000-patient Monte Carlo Simulation.RESULTS:
In plasma, the maximum concentration (Cmax ) and area under the concentration-time curve from 0 to 12 h (AUC0-12h ) were 2.21 ± 0.17 mg/L and 15.29 ± 1.13 h mg/L, respectively. In sputum, they were 2.48 ± 0.21 mg/L and 19.46 ± 1.82 h mg/L, respectively. The mean lung penetration rate was 127.27%. At the MIC ≤4 mg/L, the PTAs in plasma and sputum were 100.00%. When the MIC increased to 8 mg/L, the PTAs in plasma and sputum mostly were < 90.00% according to two criteria. WHAT IS NEW ANDCONCLUSION:
In this study, we explored PK/PD of high-dose tigecycline in plasma and sputum. From a PK/PD perspective, high-dose tigecycline had greater therapeutic outcomes in HAP treatment caused by MDRB. Antimicrobial-drug concentrations should be determined to optimize their clinical use.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
/
Antibacterianos
Tipo de estudo:
Health_economic_evaluation
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Clin Pharm Ther
Assunto da revista:
FARMACIA
/
TERAPEUTICA
Ano de publicação:
2022
Tipo de documento:
Article