Population Pharmacokinetics And Dose Optimization Of Levofloxacin In Elderly Patients With Pneumonia

PurposeThe elderly are the high incidence of pneumonia,and the aging problem of our population is becoming more serious in recent years,and the number of elderly pneumonia patients has been increasing.Levofloxacin is a third-generation quinolone antibacterial drug with a wide antibacterial spectrum,which has great antibacterial effect on both gram-positive bacteria and gram-negative bacteria.It is used in elderly patients with pneumonia widely.Levofloxacin is a concentration-dependent antibacterial drug,and excessive administration of doses will lead to an increased incidence of adverse reactions of levofloxacin,while insufficient doses will lead to poor therapeutic efficacy,and even cause resistance and treatment failure.Therefore,individualized therapy with levofloxacin in senile pneumonia patient is particularly important.The pharmacokinetic profile of elderly patients changes with age,but data on the pharmacokinetics of levofloxacin in elderly patients are limited.The objective of this study was to establish a population pharmacokinetic model of levofloxacin in elderly patients with pneumonia and to optimize individualized dosing regimens based on the model.MethodsThis is a prospective,open-label pharmacokinetic study in senile pneumonia patient.The sample collection method was opportunistic blood collection.The plasma concentration of levofloxacin was determined by high performance liquid chromatography.A population pharmacokinetic model of levofloxacin in the elderly population was established using nonlinear mixed-effect model software.Monte Carlo simulation was used for dose simulation and dose optimization of levofloxacin in the elderly.The pharmacodynamic evaluation index of levofloxacin was the area under the drug concentration-time curve/minimum inhibitory concentration.ResultsData from a total of 51 senile pneumonia patients were used for population pharmacokinetic analysis.The one-compartment model of primary elimination was most suitable for describing the population pharmacokinetic model of levofloxacin in senile pneumonia patient,and the estimated glomerular filtration rate is a covariate that has a significant impact on the model.Model validation shows that the model has good stability and predictive performance.The final model estimated the mean clearance of levofloxacin in senile pneumonia patient to be 5.26 L/h.Monte Carlo dose simulation results showed that for senile pneumonia patient,the minimum inhibitory concentration of 2 mg/L was used,and the recommended regimen was 750 mg once a day.ConclusionIn this study,a population pharmacokinetic model of levofloxacin in elderly pneumonia patients was established,and the dose optimization of levofloxacin in the treatment of elderly pneumonia was completed through Monte Carlo dose simulation.