Pharmacokinetics of Preoperative Vancomycin

Study Overview
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Brief Summary
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A study of plasma and tissue vancomycin pharmacokinetics in pediatric surgical patients.

Detailed Description
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Background: Vancomycin is used for antibiotic prophylaxis in pediatric surgical patients without a complete understanding of plasma and soft tissue pharmacokinetics. Guidelines recommend incision within 60 minutes after administration; however, tissue concentrations of vancomycin at that early time may not be therapeutic. The Investigators conducted a study of plasma and tissue concentrations in pediatric neurosurgical and orthopedic patients to characterize intraoperative vancomycin pharmacokinetics. Patients, ages (0.1-18.8 years), undergoing posterior spinal fusion (n=30) or ventriculoperitoneal shunt placement (n=30), received intravenous vancomycin 15 mg/kg over one hour. Skin biopsies were taken at incision and skin closure. Blood samples were also collected at incision and closure; additional samples were drawn at 2- and 4-hours if patient was still in surgery. Population pharmacokinetic (PK) analysis was performed to characterize PK parameter estimates and to develop a model of intraoperative plasma and tissue vancomycin concentrations vs. time.

Official Title
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Preoperative Vancomycin Administration for Surgical Site Prophylaxis: Plasma and Soft Tissue Concentrations in Pediatric Neurosurgical and Orthopedic Patients

Conditions
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Surgical Site Infection, Vancomycin

Intervention / Treatment
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* Drug: Administration of Vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Neurosurgery patients between the ages of 31 days up to 18 years Receiving a single dose of vancomycin administered prior to surgery for cerebrospinal fluid (CSF) shunt placement or revision. Orthopedic surgical patients between the ages of 31 days up to 18 years Receiving a single dose of vancomycin administered prior to surgery for definitive spinal fusion. Exclusion Criteria: Patients already receiving vancomycin for treatment of an active infection, Patients who have a Creatinine ≥1.2, Patients who's creatinine clearance less than 50, Known chronic renal failure and are on dialysis, Patients with a known allergy to vancomycin, not including Red Man Syndrome.

Ages Eligible for Study
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Minimum Age: 31 Days
Maximum Age: 18 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Administration of Vancomycin<br>Administration of Vancomycin 15 mg/kg over 1 hour prior to surgical incision | Drug: Administration of Vancomycin<br>* Intravenous Vancomycin Administration<br>* Other names: Vancomycin Hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics Analysis: V˅c | Volume of the central compartment. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed). | 
| Pharmacokinetics Analysis: V˅2 | Volume of the peripheral compartment Typical value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed). | 
| Pharmacokinetics Analysis: Q | Intercompartmental clearance between central compartment (Vc) and peripheral compartment (V2) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed). | 
| Pharmacokinetics Analysis: Cle | Elimination clearance. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed). | 
| Pharmacokinetics Analysis: sf˅V2 | Scaling Factor for Body weight covariate for V2 (Volume of the peripheral compartment) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed). | 
| Pharmacokinetics Analysis: sf˅Cle | Scaling Factor for Body weight covariate for Cle (elimination clearance) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed). | 
| Pharmacokinetics Analysis: K˅skin0 | Accounts for the equilibration rate between plasma and skin. Typical Value should be read as 3.6E-05. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed) | 
| Pharmacokinetics Analysis: PC | Partition coefficient, models skin drug concentration between plasma and skin. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed) | 
| Pharmacokinetics Analysis: δ ˅R-plasma | Proportional or relative intrasubject variability for plasma data Typical Value. There is no unit of measure for this measurement. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed) | 
| Pharmacokinetics Analysis: δ ˅A-skin | Additive intrasubject variability for skin data Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed) |