Pharmacokinetics and drug concentration monitoring of high-dose tigecycline in patients with septic shock / 中国药科大学学报

ABSTRACT

This article established a method for the detection of tigecycline in patients with septic shock.The column was Ultimate AQ-C1s(3.0 mm × 100 mm,3 μm).The mobile phase was water (0.2％ Formic acid,5 mmol/L ammonium acetate)-acetonitrile,gradient elution,the ion transitions were performed under ESI positive model at m/z 586.4→513.3 (tigecycline),m/z 338.2→296.0 (linezolid).Calibration curves of tigecycline showed good linear regression in the range of (50.15-2 006) ng/mL.The intra-day and inter-day RSD were below 15％.Plasma sample kept good stability.The cmax and AUC0-12 h of tigecycline in septic shock patients were (1.97 ±0.87) μg/mL and (9.10 ±3.58) mg.h/L.The results showed that after giving high doses tigecycline to patients with septic shock caused by multidrug-resistant strains,the AUC was not significantly higher in severe nosocomial pneumonia patients with conventional doses,and lower than the AUC of sepsis patients at the same dose,did not achieve the desired bactericidal effect.Maybe with the high hemodynamics in septic shock patients increased tigecycline glomerular filtration,and systemic infection leads to increased capillary permeability combined with interstitial edema,so that the distribution of the drug volume increases.In combination with the above,it is recommended that the recommended dose range for tigecycline in patients with septic shock caused by multidrug-resistant strains should be between 150 and 200 mg,and the concentration of tigecycline in the critically ill patients should be monitored and patients in different stages of the disease in a timely manner to adjust the dose.