Effect of Weight and/or Obesity on Ethambutol Drug Concentrations

Study Overview
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Brief Summary
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This study is designed to measure drug concentrations in the blood of healthy volunteers administered a single dose of ethambutol. Our hypothesis is that volunteers with a body mass index (BMI) 25-40 kg/m2 will remove ethambutol more quickly from the blood than leaner volunteers, and those with a BMI > 40 kg/m2 will have even greater clearance than those who are leaner.

Official Title
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Population Pharmacokinetics Analysis of Ethambutol in Overweight and Obese Volunteers

Conditions
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Obesity, Tuberculosis

Intervention / Treatment
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* Drug: Ethambutol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female volunteers, age 18 years of age or older, of all racial and ethnic origins. English and/or Spanish speaking volunteers are eligible to participate. We are recruiting 6 normal weight (BMI <25 kg/m2), 6 obese (BMI 25-40 kg/m2), and 6 extremely obese (BMI > 40 kg/m2) for this study. Half of each group will be male, the other half will be female. Exclusion Criteria: Creatinine clearance < 70 ml/min as estimated by the Cockcroft-Gault equation. Pregnant or nursing or unwilling to use a reliable contraception method during the study period. The effects of ethambutol on pregnancy are unknown. In addition, the metabolic changes that accompany pregnancy may alter the concentration-time profile of ethambutol, so that the pregnancy and post-partum state would be a confounding variable. Abnormal liver function tests: transaminases >10 time the upper limit of normal, alkaline phosphatase > 5 time the upper limit of normal, total bilirubin >5 time the upper limit of normal. History of allergy to ethambutol. Ethambutol is contraindicated for any reason. Suspected or documented mycobacterial infection. History of gout.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ethambutol<br>All volunteers in each category will receive a single dose of oral ethambutol based on American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of American (ATS/CDC/IDSA) TB treatment guidelines.1 We will not use any doses higher than the maximum dose recommended for daily administration by the current ATS/CDC/IDSA TB guidelines (which use ideal body weight for dosing): 40-55kg: 800 mg (two 400 mg tablets) 56-75kg: 1,200 mg (three 400 mg tablets) 76-90kg: 1,600 mg (four 400 mg tablets) > 90 kg: No dosage recommendations so these volunteers will only receive 1,600 mg (four 400 mg tablets) | Drug: Ethambutol<br>* All volunteers in each category will receive a single dose of oral ethambutol based on American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of American (ATS/CDC/IDSA) TB treatment guidelines.1 We will not use any doses higher than the maximum dose recommended for daily administration by the current ATS/CDC/IDSA TB guidelines (which use ideal body weight for dosing): 40-55kg: 800 mg (two 400 mg tablets) 56-75kg: 1,200 mg (three 400 mg tablets) 76-90kg: 1,600 mg (four 400 mg tablets) > 90 kg: No dosage recommendations so these volunteers will only receive 1,600 mg (four 400 mg tablets)<br>* Other names: Myambutol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Clearance of Ethambutol |  | Blood samples will be collected over a 24 hour period (0, 2, 6, 11, 18, and 24 hours) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Pharmacokinetics, Pharmacodynamics, Dose individualization, Tuberculosis