PK/PD Study On Tigecycline In Severely Infected Patients

Objective:In order to provide reference for drug quality and rational use,a pharmacokinetics/pharmacodynamics(PK/PD)study was performed on severely infected patients,who were administrated 100 mg q12h of tigecycline in ICU of a hospital.Methods:The severely infected patients of ICU who were administrated tigecycline intravenously with the dose of 100 mg q12h were collected in this study.The blood samples were collected within 12 hours.CRRT ultrafiltrate were also collected if any patients were treated with CRRT simultaneously.Time for blood and CRRT ultrafiltrate samples collection were 1 h,1.5 h,2 h,4 h,6 h,and 12 h after the first dose of tigecycline administration.2 ml of each blood samples were centrifuged immediately and preserve the upper plasma in a-80? refrigerator before measured,the ultrafiltrate were the same.The drug concentration in each sample was detected by HPLC.The pharmacokinetic parameters were simulated and calculated with DAS 2.0,as well as the the area under the bacteriostatic curve AUIC(AUC0.24/MIC).The rate of reaching standard AUIC,clinical efficacies,bacterial clearance rates and incidence of adverse reactions were evaluated according to published data.Results:In our study,17 cases of patients were enrolled,with 8 patients in the CRRT group and 9 patients in non-CRRT group.All patients had combined antibacterial agents at the time.The PK/PD was evaluated as reaching the standard if the AUIC?6.96 for peritoneal infection,AUIC?17.9 for skin infection,and AUIC?12.8 for lung infection.1.Non-CRRT group:Cmax=1.00±0.66 ?g·mL-1,Cmin=0.20±0.12 ?g·mL-1,AUC0-24=22.12±14.46,the total rate of reaching the standard AUIC was 55.6%,the clinical efficiency was 55.6%,the bacterial clearance rate was 77.8%,and 3 patients had suspected adverse effects of tigecycline(33.3%).2.CRRT group:Cmax=0.96±0.31?g·mL-1,Cmin=0.22±0.12 ?g·mL-1,AUC0-24=19.90±8.14,the total rate of reaching the standard AUIC was 28.7%,the clinical efficiency was 25%,the bacterial clearance rate was 25%,and 2 patients had suspected adverse effects of tigecycline(25%).3.After comparing the two groups,we found that the differences of two groups'Cmax,Cmin and AUC have no statistical significance;the differences of the two groups'clinical efficiency and bacterial clearance rate have no statistical significance.Conclusion:1.The tigecycline plasma concentration in our study was similar to the existing research data,but individual differences were significant.We suggest to monitor tigecycline plasma concentration and to individualize administration according to PK/PD models.2.CRRT can filter out a few part of tigecycline in blood,but in our study,the difference between Cmax,Cmin,AUC and CL in two groups have no statistical significance.More researches are needed in future.3.The plasma concentration between the two groups were similar,but the rate of clinical efficiency and bacterial clearance were low in both two groups.In addition,the rates of reaching standard AUIC,clinical efficiency and bacterial clearance in CRRT group were all lower than 30%.15 of the 17 patients enrolled in this study had APACHE ? scores?20,and CRRT group has higher APACHE ? scores(34.75±9.91),which means the clinical efficacy and bacterial clearance of tigecycline were highly related to APACHE ? scores.In conclusion,a low tigecycline plasma concentration of was observed in severely infected patients,with obvious individual differences.In view of the correlationship between plasma concentration and clinical efficacy,therapeutic drug monitoring of tigecycline is necessary,and adjusting dosage according to PK/PD models could have better clinical effect.