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Pharmacokinetics of an Aminoglycoside in Hemodialysis Patients.

Information source: University Hospital, Limoges
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Renal Failure Chronic Requiring Hemodialysis

Intervention: Gentamicin (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: University Hospital, Limoges

Official(s) and/or principal investigator(s):
Pierre MARQUET, MD, Principal Investigator, Affiliation: CHU LIMOGES

Overall contact:
Franck SAINT MARCOUX, Phone: 05 55 05 61 40

Summary

Aminoglycosides are widely used for the treatment of Gram-negative bacilli and Staphylococcus aureus infections because of their effectiveness and low cost. Nevertheless, many aspects of their optimal use in hemodialysis patients remain unsolved and little is known about their pharmacokinetics in this context. The current practice for prescribing aminoglycosides to these particular patients consists in giving after each hemodialysis session about half the dose usually given to patients with normal renal function. However, theoretical considerations and emerging clinical data suggest that this may not be the most beneficial dosing regimen as efficient peak concentrations are often not attained and the occurrence of ototoxicity and nephrotoxicity is still frequent.

Clinical Details

Official title: Pharmacokinetics of an Aminoglycoside in Hemodialysis Patients.

Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Primary outcome: Concentration curves of gentamicin

Detailed description: Recent evidence about the pharmacokinetics and pharmacodynamics of aminoglycosides strongly supports administration of aminoglycosides before, rather than after, hemodialysis. Therapeutic drug monitoring using pharmacokinetic modeling is currently used in non-hemodialysis patients. However, the PK tools employed are not suitable to dialysis patients. For aminoglycosides, the ratio of peak to Minimal Inhibitory Concentration (MIC) has been shown to be the parameter that best correlates with clinical efficacy, whilst prolonged exposure to high concentrations have been related to either nephrotoxicity or ototoxicity. Additionally, aminoglycosides are mostly excreted as unchanged drugs in urine and their clearance is directly proportional to the glomerular filtration rate. The elimination half-life of aminoglycosides is approximately 1. 5-3 hours in adults with normal renal function, but is greatly prolonged up to 36-70 hours in patients with end-stage renal failure. In a standard patient, aminoglycosides are administered as a single dose, over a short time interval, to obtain an elevated blood peak concentration (the effective level). The next injection is not administered before 24 hours, to allow the patient to wash out the aminoside and to minimize the residual blood concentration (the toxic level). The aim here is to maximize the peak concentration during a fair amount of time (by repeating the peaks) and to minimize the overall drug exposure, responsible for the toxicity. For the renal impaired patient, our hypothesis is that the hemodialyzer can be regarded as a kidney. Thus, the administration of the aminoside at the beginning of the hemodialysis could lead to profiles of elimination comparable to those observed in normorenal patients. The research aims at performing a population pharmacokinetic (POPPK) study of gentamicin when given to hemodialysis patients.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- age upper to 18 years

- Patients hospitalized in the "Service de Néphrologie - Hémodialyse, Transplantations,

CHU de Limoges"

- Patients requiring chronic hemodialysis

- Patients requiring a treatment by aminoglycosides

- Patients willing to give their written informed consent for their participation to

the study

- Patients affiliated to the French social security system or equivalent

Exclusion Criteria:

- Patients under legal protection

- Patients unable or unwilling to provide informed consent and not under legal

protection

- Patients deprived of liberty

- Contraindications to gentamicin

- Pregnant or breast-feeding women or women of childbearing potential without efficient

contraception (based on declaration)

- Patients with any altered mental status or any psychiatric condition that would

interfere with the understanding of the study

- Patients enrolled in another clinical trial testing drugs or therapeutic strategies

Locations and Contacts

Franck SAINT MARCOUX, Phone: 05 55 05 61 40

CHU LIMOGES - Laboratoire de Pharmacologie, Limoges 87042, France; Recruiting
Frank SAINT MARCOUX, Phone: 05 55 05 61 40
Caroline MONCHAUD, Phone: 05 55 05 61 40
Pierre MARQUET, MD, Principal Investigator

CHU LIMOGES - Service Néphrologie, Limoges 87042, France; Recruiting
Marie ESSIG, MD, Phone: 05 55 05 66 18
Marie ESSIG, MD, Sub-Investigator

Additional Information

Starting date: October 2013
Last updated: July 10, 2014

Page last updated: August 23, 2015

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