PK/PD study of tigecycline in severely infected patients with continuous renal replacement therapy.

ABSTRACT

OBJECTIVE: The aim of this study was to analyze the pharmacokinetics/pharmacodynamics (PK/PD) of higher-dose tigecycline (100 mg q12h) in severely infected intensive care unit (ICU) patients receiving continuous renal replacement therapy (CRRT). MATERIALS AND METHODS: In this prospective single-center observational study, severely infected patients receiving intravenous tigecycline were enrolled. They were divided into a CRRT group (7 cases) and a non-CRRT group (9 cases). The blood samples and CRRT ultrafiltrate were collected. The drug concentration in each sample was determined by a HPLC-UV method. The pharmacokinetic parameters were simulated and calculated with DAS 2.0. The PK/PD parameters were evaluated according to published data. The registration number of this study is NCT02931526 in ClinicalTrials.gov. RESULTS: In the non-CRRT group, Cmax, Cmin, and AUC0-24 were 1.00 ± 0.66 µg×mL-1, 0.20 ± 0.12 µg×mL-1, and 22.12 ± 14.46 µg×h×mL-1, respectively. The clinical efficiency was 55.6%, and the bacterial clearance rate was 77.8%. In the CRRT group, Cmax, Cmin, and AUC0-24 were 0.96 ± 0.31 µg×mL-1, 0.22 ± 0.12 µg×mL-1, and 19.90 ± 8.14 µg×h×mL-1, respectively. The clinical efficiency was 28.6%, and the bacterial clearance rate was 28.6%. The individual differences of tigecycline plasma concentrations in our study were widely variable, and the differences of the two groups' PK/PD parameters had no statistical significance (p < 0.05). CONCLUSION: CRRT may have had little influence in tigecycline metabolism in our study, and therapeutic drug monitoring needs to be introduced for critically ill patients because of various pharmacokinetic parameters.