Population Pharmacokinetics of Lassila Tazobactam in Patients After Aortic Dissection

• Conditions: Lung Infection; Aortic Dissection

• Registration Number: NCT05349305
• Lead Sponsor: The Second Hospital of Shandong University

Brief Summary

The individualized drug use research on optimizing piperacillin tazobactam for CRRT of hospital-acquired pulmonary infection after cardiopulmonary bypass is still in the initial stage at home and abroad, lacking systematic research data. With the help of the population pharmacokinetic model, it can help clinicians to formulate individualized drug administration plans for such patients and provide methodological and data support for precise treatment. The rational use of piperacillin tazobactam will play an important role in reducing the use of carbapenems and curbing the occurrence of drug resistance.

Detailed Description

The incidence of acute renal failure after aortic dissection can be as high as 30%. In order to reduce mortality, most patients need continuous renal replacement therapy (CRRT). The concentration of antimicrobial drugs in patients receiving CRRT is often lower than the treatment level, which leads to treatment failure. The drug clearance rate of critically ill patients may change every day and it is difficult to estimate, especially when the renal function deteriorates and CRRT begins.

As a time-dependent antimicrobial drug, increasing the% t \> MIC of piperacillin tazobactam is closely related to ensuring clinical efficacy. However, the molecular weight of piperacillin tazobactam is less than 2000 d, which can easily pass through the filter membrane. All CRRT methods have the same clearance rate. Meanwhile, the binding rate of piperacillin and tazobactam to plasma protein is only about 30%, which is easy to clear through CRRT. As a result, the curative effect of piperacillin tazobactam in treating hospital-acquired pneumonia after aortic dissection is not good according to the conventional dosage and administration. More and more doctors will consider choosing carbapenems as soon as possible, which is related to national health.

Therefore, the traditional pharmacokinetic study is no longer applicable, and it can't provide a basis for clinical determination of individualized drug use plan of piperacillin and tazobactam, while the population pharmacokinetic study can effectively solve this problem. The frequency of blood collection from patients is low (usually 2 \~ 4 blood collection points), which is the most advanced method for individualized drug use research in the world at present \[10\]. Methods The Nonlinear mixed effect Model (non-MEM) was used to calculate the average and variability of pharmacokinetic parameters in patients, and the synergistic effect of patient factors (such as age and weight) on pharmacokinetic parameters could be evaluated, thus providing a reliable basis for formulating individualized and accurate drug administration plan and improving the success rate of anti-infection.

Study Timeline

• Status Verified: 2022-04
• Study First Submitted: 2022-04-19
• Study First Submitted QC: 2022-04-24
• Last Update Submitted: 2022-04-24
• Study First Posted: 2022-04-27
• Last Update Posted: 2022-04-27
• Study Start: 2022-04-30
• Primary Completion: 2023-12-31
• Study Completion: 2024-07-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Cardiopulmonary bypass during aortic dissection， Lung infection， Continuous renal replacement therapy

Exclusion Criteria

Intracranial infection, Urinary tract infection

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
blood concentration	Up to 8 hours after administration	Blood concentration of piperacillin and tazobactam in whole period after administration