Pharmacokinetic/Pharmacodynamic Study of Tigecycline in Elderly Patients with Upper Gastrointestinal Perforation Complicated with Intra-abdominal Infection

This study aimed to investigate drug concentration in plasma and peritoneal drainage fluid of patients with gastrointestinal perforation treated with tigecycline and provide a reference for the clinical and rational use of tigecycline. A total of 11 patients were included in this study. After an intravenous drip of 100 mg tigecycline, venous blood and peritoneal drainage fluid were collected from patients at different time points. Drug concentration was determined using HPLC. Pharmacokinetic parameters were calculated by using a non -compartment model. The probability of area under the curve (AUC)((0-24))/minimum inhibitory concentration (MIC) >= 6.96 target for tigecycline was calculated through Monte Carlo simulation. The AUC of plasma and peritoneal drainage fluid was 9.51 +/- 0.97 and 7.64 +/- 0.86 h.mu g/mL, respectively. The average penetration rate of tigecycline in peritoneal drainage fluid was 80.34%. When MIC <= 1 mu g/mL, the probability of target attainment (PTA) for tigecycline in plasma and peritoneal drainage fluid was > 90%. When MIC increased to 2 pg/mL, the PTA in plasma was > 90%. However, when MIC further increased to 4 pg/mL, the PTA in plasma and peritoneal drainage fluid was < 90%. This study is the first to investigate the pharmacokinetics/pharmacodynamics of tigecycline in plasma/peritoneal drainage fluid of patients with upper gastrointestinal perforation complicated with intra-abdominal infection, revealing that when MIC >= 2 mg/L, treatment is at risk of failure.