Effect of Weight and/or Obesity on Sulfamethoxazole and Trimethoprim Concentrations

This study is designed to measure drug concentrations in the blood of volunteers administered
a single oral dose of sulfamethoxazole and trimethoprim. The volunteers to be enrolled will
not have ear infections, urinary tract infections, bronchitis, traveler's diarrhea,
Pneumocystis carinii pneumonia, or any other bacterial infection. This is a single center
study. A total of 36 adult volunteers will be consented for the study at the Clinical and
Translational Research Center (CTRC). Volunteers will be recruited using IRB approved fliers.
Volunteers will be admitted to the CTRC for an overnight stay. Half will be female and half
male. Twelve volunteers will have a body mass index (BMI) less than 25 kg/m2, twelve will
have a BMI 25-40 kg/m2, and twelve will have a BMI greater than 40 kg/m2. Volunteers will
have height and weight measured after they have consented to participate. All volunteers will
receive a single oral dose of sulfamethoxazole and trimethoprim of 1600 mg/320 mg. The
volunteers will have blood drawn via an intravenous catheter just prior to the dose, and then
at 1, 2, 4, 8, 12, and 24h after the drug dose. The intravenous catheter is then removed
after the 24h blood draw, and the volunteer is discharged from the study.

Inclusion Criteria:

- Male and female subjects, age >18 years, of all racial and ethnic origins.

- We are recruiting 12 normal or underweight (BMI <25kg/m2), 12 overweight or obese (BMI
25-40 kg/m2), and 12 extremely obese (BMI > 40 kg/m2) for this study. This index is
calculated using the volunteer's height and weight (Formula: weight (lb) / [height
(in)]2 x 703). Half of each group will be male; the other half will be female.

Exclusion Criteria:

- Pregnant or nursing or unwilling to use a reliable contraception method during the
study. The effects of sulfamethoxazole and trimethoprim on pregnancy are unknown. In
addition, the metabolic changes that accompany pregnancy may alter the
concentration-time profile of sulfamethoxazole and trimethoprim, so that the pregnancy
and post-partum state would be a confounding variable.

- Abnormal liver function tests: transaminases>10 times upper limit of normal, Alkaline
phosphatase>5 times upper limit of normal, total bilirubin>5 times upper limit of
normal.

- History of allergies to sulfones, sulfonamides or trimethoprim.

- Sulfones, sulfonamides or trimethoprim are contraindicated for any reason.

- Volunteers unwilling to comply with study procedures.

- Current suspected or documented ear infection, urinary tract infection, bronchitis,
traveler's diarrhea, Pneumocystis carinii pneumonia, or any other bacterial infection.

- Volunteers with colon resection, gastric bypass, lap band, or any other conditions
inhibiting gastric absorption of drug.

- Current or previous participation within 28 days of enrollment in another research
study that involves the use of medication, contrast, or any other compound that may
alter blood count and/or blood chemistry (liver function, kidney function or
electrolyte balance), unless waved by PI.

- Donation of 450mL (one unit) of blood or more within 8 weeks (56 days) prior to study
enrollment, unless waved by PI.

- Current use of medications contraindication with sulfamethoxazole/trimethoprim use:
Bepridil, Cisapride, Dofetilide, Levomethadyl, Mesoridazine, Pimozide, Terfenadine,
and Thioridazine. Other medications will be screened by study investigators to ensure
the safety of research participants and maintain the quality of the study.