Pharmacokinetics of imipenem in patient receiving high- volume hemofiltration

Pharmacokinetics is significantly altered in critically ill patients receiving high volume hemofiltration (HVHF). This is an important issue for antimicrobials. Imipenem is a carbapenem antibiotic with broad spectrum activity and time-dependent effect. The time-dependent concentration must exceed the minimum inhibitory concentratio (MIC)of at least 50% of dose interval.

The aim of this study is to determine the effect of HVHF on imipenem pharmacokinetics and develop a dosage adjustment to reach appropriate serum concentration of this antibiotic.

High performance liquid chromatography (HPLC) method for separation and determination of imipenem in plasma and hemofiltration fluid was developed. Ten critically ill patients receiving HVHF treated with imipenem 0,5 mg/8h were included in this study. Imipenem concentrations were measured at timed intervals to determine pharmacokinetics parameters and were studied whether imipenem was above MIC.

Imipenem was detected by UV absorbance at 300 nm with no interfering peaks. The limit of quantification was 0,01 ug/mL. The method has good sensitivity, precision and accuracy. The pharmacokinetics profile showed that only 32% of administration interval was above MIC of imipenem for susceptible pathogens. The fraction cleared by HVHF was 45%, whis is clinically important. The results suggest that HVHF contributes to accelerate imipenem elimintion and prevents serum concentration to ensure efficacy of this antibiotic. Dosage adjustment seems to be required in this condition. Constant therapeutic drug monitoring in critically ill patients is necessary and this HPLC method may be helpful to improve clinical outcomes in these patients.

In critically ill patients receiving High Volume Hemofiltration (HVHF), pharmacokinetics is significantly altered. This is an important issue for antimicrobials. Imipenem is a carbapenem antibiotic with broad spectrum activity and time-dependent effect. The time dependent concentration may exceed the minimum inhibitory concentration(MIC)concentration of at least 50% of dose interval.

The aim of this study was to determine the effect of HVHF on imipenem pharmacokinetics and develop a dosage adjustment to reach appropriate serum concentration of this antibiotic.

HPLC method for determination and quantification of imipenem in plasma and hemofiltration fluid was developed. Ten critically ill patients receiving HVHF treated with imipenem 0,5 g/8 h were included in this study. Imipenem concentrations were measured at timed intervals to determine pharmacokinetics parameters and we studied whether imipenem was above MIC.

Imipenem was detected by UV absorbance at 300 nm with no interfering peaks. The limit of quantification was 0,01 ug/mL. The method had good sensitivity, precision and accuracy. The pharmacokinetics profile shown that the time above MIC of imipenem for susceptible pathogen was only 32% of administration intervals. The fraction cleared by HVHF was 45%, wich is clinically important. These results suggest that HVHF contributes to accelerate imipenem elimination and prevents serum concentration to ensure efficacy of this antibiotic. Dose adjustment seems to be required in this condition. Constant therapeutic drug monitoring in critically ill patients is necessary and this HPLC method may be helpful to improve clinical outcomes in these patients.