Pharmacokinetics And Pharmacodynamics Of Moxifloxacin Sodium Chloride Injection In Patients With Lower Respiratory Tract Infection

Objective:(1) To investigate the pharmacokinetics of moxifloxacin in patients with lowerrespiratory tract infection, providing reference to its reasonable clinical application.(2) To analysis and evaluate the pharmacodynamics of moxifloxacin in patients;the minimal inhibitory concentrations (MIC) was also assayed with the main pathogenicbacteria in sputum specimens of patients with lower respiratory tract infection.Methods:(1) The moxifloxacin’s concentrations in plasma were analysed by HPLC. Thechromatographic column was Diamonsil C18column(5μm,150mm*4.6mm).The mobilephase was composed with potassium dihydrogen phosphate (containing0.1%triethylamine, pH3.0)-acetonitrile-methanol(65:15:20,v/v/v). The flow rate was1mL·min-1. Detection wavelength was296nm, and column temperature was30℃.Sample quantity was40μL. For higher accurate of the analysis, the internal standardmethod was applied in the HPLC analysis.This research was based on multi-dose and single period design. Eighteen cases oflower respiratory tract infection treated with moxifloxacin were included，the age is18to45years, nine men and nine women. Patients could not have taken any antibiotic inthe previous two weeks, and did not participate in any clinical trials in the previousthree months. The patients should also be with no history of drug allergy(especially tothe Quinolones). Physical and laboratory examination were performed before the thepatients were included. The18eligible patients were given400mg moxifloxacin once aday at8:00am, i.v.drip over90min. During the experiment, patients were prohibiteddrinking alcohol, tea, or caffeinated beverages. Patients also were also required avoidingstrenuous activities and excessive sun. Safety and tolerability were observed during the whole experiment. To each patient, five microliters blood was extracted on1.5h afteri.v. drip、0h before the next i.v. drip and1.5h after the third administration frommedian cubital vein. Moxifloxacin in plasma was quantitative determined by HPLC.(2) This research was based on multi-dose, single period design, and self-controlstudy. The therapeutic effect of moxifloxacin was estimated from clinical andetiological points of view. According to the guiding principle, evaluate patients’ clinicalsymptoms and signs, the clinical therapeutic effect was classified as cure, markedlyimprovement, improvement, and no improvement. Etiological is divided into in vivoand in vitro, sputum specimens from patients were cultured before and after thetreatment. The results of culture were classified as clearance, supposed clearance, partlyclearance, no clearance, and replacement. As to the in vitro susceptibility,205strains ofpathogenic bacteria, including haemophilus influenzae, pneumonia klebsiella bacillus,staphylococcus aureus, streptococcus pneumoniae, and mycoplasma pneumoniae whichwere isolated from patients with lower respiratory tract infection, were used todetermine the MIC of moxifloxacin.Results:(1)The retention time of moxifloxacin was about5.7min in HPLC analysis. Linearrange was0.1-12.8mg/L with a typical regression equationC=0.061011As/Ai-0.00053(r=0.9989). The minimum quantitative limit was0.1mg/L.This methodology reached the determination requriments from the “Principles ClinicalPharmacokinetic Study of Chemical Drugs”.(2) Peak concentration, trough concentration, steady state plasma concentrationwere (3.69±0.06)mg L-1,(1.44±0.11)mg L-1, and (4.53±0.07)mg L-1respectively, afterintravenous drip of moxifloxacin sodium chloride injection,. During the experiment, noadverse reaction was found in patients. All of these showed that moxifloxacin was welltolerated in patients.(3) Among the18cases,10patients were suffered from pneumonia, in which fivewere co-infection with bronchial asthma. After the whole program,15cases were cured,in which one was marked effective, and two were improved, with the total clinicaleffective rate88.9%. To all patients, most of the clinical symptoms and signs improvedor alleviated obviously after three days’ treatment.Before treatment,18strains were isolated from sputum specimens, with thepositive rates66.7%. The main pathogenic bacteria was klebsiella pneumoniae, withaccounts for38.9%. After treatment, the bacteria clearance reached88.9%, which showed good therapeutic effect. Results from in vitro sensitive ananlysis test showedthat bacteria were sensitive to moxifloxacin.Conclusions:Peak and trough concentration of moxifloxacin in patients could reach high levelafter single-dose iv.drip, and the concentrations were much higher than MIC. Highconcentration of moxifloxacin in blood contributes to the successful treatment inpatients with lower respiratory tract infections. Patients obtained excellent clinical andbacterial efficiency after treatment. In vitro sensitive analysis showed that the mainpathogenic bacteria isolated from patients with lower respiratory tract infection weresensitive to moxifloxacin. To sum up, moxifloxacin is deserved to the treatment oflower respiratory tract infections.