Effect of Weight and/or Obesity on Ethambutol Drug Concentrations

Texas Tech University Health Sciences Center

Status and phase: Completed; Phase 4

Conditions: Tuberculosis; Obesity

Treatments: Drug: Ethambutol

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01048697

5UL1RR024982-02 (U.S. NIH Grant/Contract)

TTUHSC 030032

Details and patient eligibility

About

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.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

18 participants in 1 patient group

Ethambutol

Experimental group

Description:

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)

Treatment:

Drug: Ethambutol