Study Of The Determination Of Tigecycline Concentration In Human Plasma And Correlation About Tigecycline Efficacy And ADR

Objective:Tigecycline acts as the last drug to defense against bacteria,in recent years,with the controversy about its efficacy and the increasing reports of drug resistance and adverse drug reactions(ADR),this study aim to explore the correlation between basic data,physiological and pathological data,total and free plasma drug concentration of tigecycline with the efficacy and ADR in patients with severe infection,to provide rational drug reference for patients with severe infection using tigecycline.Method:1.To establish HPLC-MS/MS,ultrafiltration centrifugation combined with HPLC-MS/MS method to determinate total and free plasma concentration of tigecycline,and investigate the methodology.2.Based on the criteria,to include patients with severe infection who used tigecycline from February 2019 to January 2020 in a third-class first-class hospital.To collect basic data,physiological and pathological data,total and free plasma concentration of tigecycline,the efficacy and ADR,using SAS 9.2for relevant statistical analysis.Result:1.Both methods met the requirements of drug analysis in vivo.The standard curve equation of total plasma concentration of tigecycline was Y=0.00314 X-0.00231(r~2=0.9997),and the linearity was good in the range of 20-1200 ng/mL.The standard curve equation of free plasma concentration of tigecycline was Y=0.00636X+0.0092(r~2=0.9998),and the linearity was good in the range of 3.6-360 ng/mL.54patients were included in this study,all from the department of hematology,25 males and 29 females.The average total plasma concentration of tigecycline was(128.5±57.6)ng/mL.The average free plasma concentration of tigecycline was(8.3±7.55)ng/mL.31patients were effective,23 were ineffective,and 18 patients had ADR of tigecycline.3.The efficacy of tigecycline were significantly related to the gender(P=0.0021),cardiovascular related disease(P=0.0001),critically illness(P=0.0128)and total plasma concentration of tigecycline(P<0.0001).The ADR of tigecycline were significantly related to the sex of the patient(P=0.0121),critically illness(P=0.0157),the dose of tigecycline(P=0.0169)and the change of total protein(P=0.0161).Conclusion:1.This study successfully established methods to determinate total and free plasma concentration of tigecycline.2.Clinical should pay more attention to the efficacy of tigecycline in elderly patients with cardiovascular diseases,other underlying diseases and critically ill patients,be alert to appear ADR of tigecycline in women,using high-dose tigecycline and critically ill patients.3.It is recommended to maintain the steady-state plasma concentration of tigecycline for patients with severe infection in the range of 85-150 ng/mL because of better efficacy,while the free drug concentration has no effect on the efficacy and ADR of the patients.