Linjie Dou1, Dandan Meng1, Yalin Dong1, Lihong Chen2, Xinyan Han1, Di Fan1, Haiyan Dong3. 1. Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China. 2. Department of International Medical Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China. 3. Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: donghy@mail.xjtu.edu.cn.
Abstract
BACKGROUND: Significant alterations in the pharmacokinetic characteristics of linezolid are often seen in sepsis patients. The study aimed to identify a target pharmacokinetics/pharmacodynamics (PK/PD) index of the efficacy of linezolid treatment, and to estimate the optimum dosage regimen of linezolid in sepsis patients. METHODS: The PK data were modeled using the one-compartment model, which determined the target PK/PD index for successful treatment by logistic regression. The probability of thrombocytopenia was identified by establishing a logistic model. Different dosing regimens were evaluated using Monte Carlo simulation. RESULTS: Reaching 80% bacterial eradication required an AUC24/MIC of 100, which defined the therapeutic target. The proposed regimen to attain a cumulative fraction of response ≥80% was 800 mg/12 h (safety probability 66.8%) for sepsis patients with normal renal function or mild kidney damage. By contrast, the target cumulative fraction of response was attained with a standard dosing regimen in sepsis patients on continuous renal replacement therapy [600 mg/12 h (safety probability 49.7%)]. CONCLUSIONS: This study identified different dosing strategies to achieve target linezolid PK/PD values according to whether sepsis patients were treated with continuous renal replacement therapy. Due to the high incidence of thrombocytopenia in sepsis patients on continuous renal replacement therapy, therapeutic drug monitoring should be encouraged for optimizing linezolid exposure in sepsis patients.
BACKGROUND: Significant alterations in the pharmacokinetic characteristics of linezolid are often seen in sepsispatients. The study aimed to identify a target pharmacokinetics/pharmacodynamics (PK/PD) index of the efficacy of linezolid treatment, and to estimate the optimum dosage regimen of linezolid in sepsispatients. METHODS: The PK data were modeled using the one-compartment model, which determined the target PK/PD index for successful treatment by logistic regression. The probability of thrombocytopenia was identified by establishing a logistic model. Different dosing regimens were evaluated using Monte Carlo simulation. RESULTS: Reaching 80% bacterial eradication required an AUC24/MIC of 100, which defined the therapeutic target. The proposed regimen to attain a cumulative fraction of response ≥80% was 800 mg/12 h (safety probability 66.8%) for sepsispatients with normal renal function or mild kidney damage. By contrast, the target cumulative fraction of response was attained with a standard dosing regimen in sepsispatients on continuous renal replacement therapy [600 mg/12 h (safety probability 49.7%)]. CONCLUSIONS: This study identified different dosing strategies to achieve target linezolid PK/PD values according to whether sepsispatients were treated with continuous renal replacement therapy. Due to the high incidence of thrombocytopenia in sepsispatients on continuous renal replacement therapy, therapeutic drug monitoring should be encouraged for optimizing linezolid exposure in sepsispatients.
Authors: Francesca Conradie; Tatevik R Bagdasaryan; Sergey Borisov; Pauline Howell; Lali Mikiashvili; Nosipho Ngubane; Anastasia Samoilova; Sergey Skornykova; Elena Tudor; Ebrahim Variava; Petr Yablonskiy; Daniel Everitt; Genevieve H Wills; Eugene Sun; Morounfolu Olugbosi; Erica Egizi; Mengchun Li; Alda Holsta; Juliano Timm; Anna Bateson; Angela M Crook; Stella M Fabiane; Robert Hunt; Timothy D McHugh; Conor D Tweed; Salah Foraida; Carl M Mendel; Melvin Spigelman Journal: N Engl J Med Date: 2022-09-01 Impact factor: 176.079
Authors: Ahmed E Abou Warda; Rania M Sarhan; Hussein Saeed Al-Fishawy; Ayman N Moharram; Heba F Salem Journal: Pharmaceuticals (Basel) Date: 2022-02-28