Effect of Weight and/or Obesity on Ethambutol Drug Concentrations

Overview

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.

Full Title of Study: “Population Pharmacokinetics Analysis of Ethambutol in Overweight and Obese Volunteers”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2010

Interventions

  • Drug: Ethambutol
    • 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)

Arms, Groups and Cohorts

  • Experimental: Ethambutol
    • 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)

Clinical Trial Outcome Measures

Primary Measures

  • Total Clearance of Ethambutol
    • Time Frame: Blood samples will be collected over a 24 hour period (0, 2, 6, 11, 18, and 24 hours)

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Texas Tech University Health Sciences Center
  • Collaborator
    • National Center for Research Resources (NCRR)
  • Provider of Information About this Clinical Study
    • Principal Investigator: Ron Hall, Associate Professor – Texas Tech University Health Sciences Center
  • Overall Official(s)
    • Ronald Hall, PharmD, MSCS, Principal Investigator, Texas Tech University HSC

Citations Reporting on Results

Hall RG 2nd, Swancutt MA, Meek C, Leff RD, Gumbo T. Ethambutol pharmacokinetic variability is linked to body mass in overweight, obese, and extremely obese people. Antimicrob Agents Chemother. 2012 Mar;56(3):1502-7. doi: 10.1128/AAC.05623-11. Epub 2011 Dec 12.

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