Pharmacokinetics And Pharmacodynamics Of Cefoperazone/sulbactam In Plasma And Cerebrospinal Fluid In Patients With Intraventricular Hemorrhage After External Ventricular Drains

Objective:This study was to explore cefoperazone/sulbactam in plasma andcerebrospinal fluid（CSF）in the pharmacokinetics（PK）parameters,and the different minimum bacteriostatic concentration（MIC）value %T > MIC value and standard probability（PTA）,build the pharmacokinetics pharmacodynamics of PK/PD model,which can provide theoretical basis for clinical medication and better achieve clinical treatment effect.Methods: We selected 10 cases of cerebral hemorrhage after the lateral ventricle drainage with ventilator associated pneumonia,to give 3.0g cefoperazone/sulbactam fully dissolved in 100 ml of 0.9% sodium chloride solution,the static drop after 2 hours different time points（0.5 after the treatment,1,2,3,4,6,8 and 12 h）from outside the ventricle to collect cerebrospinal fluid and blood specimens,the highly effective liquid phase color the franco-prussian methods（HPLC）was developed for the determination of cefoperazone/sulbactam in plasma/cerebrospinal fluid content,and then uses the pharmacokinetic software Winnolin6.2 to calculate the PK/PD parameters;The PTA of cefoperazone/sulbactam % T > MIC was calculated by Monte Carlo simulation based on PK/PD model with Crystal Ball software.Results: The drug concentration in plasma reached the peak 2h after intravenous injection of cefoperazone/sulbactam,C_max was 242.60± 25.41ug/mL,t1/2 was 3.07±0.27 h,AUC_0-12 h was 681.47± 49.06h·ug/mL,Cl was 2.76± 0.22L/h,and Vd was12.19±1.08L/kg.Cefoperazone/sulbactam reached the highest concentration in CSF at 3.2h±0.42 after intravenous injection,C_max was 54.23± 5.62 ug /m L,T1/2 was 7.78±1.16 h,AUC_0-12 h was 239.44± 22.35h·ug/mL.When MIC was 32ug/ml,PTA of 40%T >MIC of cefoperazone/sulbactam in plasma and cerebrospinal fluid were above 90%.Conclusions: When the MIC was 32ug/mL,the patient was treated with efoperazone/sulbactam 3.0g q12 h intravenously,which showed an effective bactericidal effect in both plasma and cerebrospinal fluid.This provides a theoretical basis for the application of antibiotics in clinical application of intracranial infection.When the MIC was 64ug/ml,cefoperazone and sulbactam can effectively kill bacteria in plasma,but the treatment effect in cerebrospinal fluid was poor,so it may be necessary to extend the infusion time and increase the drug dose or intrathecal injection of antibiotics to achieve the therapeutic effect.When the MIC was large,this regimen was not recommended to treat clinical patients.