Clearance and Pharmacokinetics of Antibiotics in Renal Replacement Therapy

Study Overview
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Brief Summary
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This is an observational study that evaluates the dialysis clearance and pharmacokinetics of antibiotics with different protein-bound levels in patients receiving renal replacement therapy. Meropenem, vancomycin and ceftriaxone are selected to represent three typical protein-bound levels, and the primary dialysis methods being studied are intermittent hemodialysis(IHD) and hemodiafiltration(HDF). During and after the dialysis, the drug levels in both plasma and spent dialysate are monitored, but no changes are made to therapy. The study will provide detailed information on the characteristics of the removal kinetics of the three antibiotics during dialysis, and evaluate whether the dosing regimens are the most appropriate to achieve therapeutic targets while minimizing the risk of toxicity.

Detailed Description
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This prospective, single-center observational study is taken to evaluate the dialysis clearance and pharmacokinetics of antibiotics with three different protein-bound levels in patients receiving renal replacement therapy. As is known that the plasma protein binding rate affects the distribution, metabolism and elimination of the drug in the body, and is also an important factor affecting the removal during dialysis, the study selects meropenem, vancomycin and ceftriaxone, of which the protein-bound levels are respectively 2%, 55% and 85%, to represent three typical protein-bound levels. The primary dialysis methods being studied are intermittent hemodialysis(IHD) and hemodiafiltration(HDF). The dialysis pattern, the antibiotic choice and its dosage for each subject are made on clinical grounds. A total of 16 milliliters of blood and 60 milliliters of spent dialysate are collected from each subject for each dialysis pattern. The study will provide detailed information on the characteristics of the removal kinetics of the three antibiotics during dialysis, and evaluate whether the dosing regimens are the most appropriate to achieve therapeutic targets while minimizing the risk of toxicity.

Official Title
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Clearance and Pharmacokinetics of Antibiotics With Different Protein-bound Levels in Renal Replacement Therapy

Conditions
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Kidney Failure

Intervention / Treatment
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* Other: Blood and spent dialysate collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With Age from 18 to 85 years old. With weight from 50 to 75 kilograms. Requiring dialysis including intermittent hemodialysis(IHD) or hemodiafiltration(HDF). Receiving meropenem, vancomycin or ceftriaxone based on clinical grounds. Exclusion Criteria: Patient is during pregnant or lactation period. Patient is allergic to meropenem, vancomycin or ceftriaxone. Severe hypoproteinemia (serum total protein<=45g/L) or severe hypoalbuminemia（serum albumin<20g/L). Severe liver dysfunction（ALT>200U/L or AST>200U/L). The patient himself or his immediate family refuses to sign the informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Meropenem<br>Patients requiring dialysis and receiving meropenem for infection or suspended infection. | Other: Blood and spent dialysate collection<br>* A certain amount of blood and spent dialysate are collected during and after dialysis for quantification of drug concentration.<br>|
| Vancomycin<br>Patients requiring dialysis and receiving vancomycin for infection or suspended infection. | Other: Blood and spent dialysate collection<br>* A certain amount of blood and spent dialysate are collected during and after dialysis for quantification of drug concentration.<br>|
| Ceftriaxone<br>Patients requiring dialysis and receiving ceftriaxone for infection or suspended infection. | Other: Blood and spent dialysate collection<br>* A certain amount of blood and spent dialysate are collected during and after dialysis for quantification of drug concentration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dialytic clearance (K_total) | The total drug amount removed by dialysis | During the session of dialysis, up to 4 hours | 
| Area under the concentration-time curve (AUC) | AUC based on plasma concentration during dialysis | During the session of dialysis, up to 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rebound of plasma concentration (Rebound_1h%) | The rebound rate of plasma concentration 1 hour after dialysis | At the end of dialysis and an hour after dialysis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Failure, Pharmacokinetics, Antibiotics