The Effect of Concomitant Administration of Erythromycin and Diltiazem on CYP3A Activity in Healthy Volunteers
Information source: Indiana University
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Intervention: Erythromycin (Drug); Diltiazem (Drug)
Phase: Phase 4
Sponsored by: Indiana University School of Medicine
Official(s) and/or principal investigator(s):
Stephen D Hall, PhD, Principal Investigator, Affiliation: Indiana University
We, the researchers at the Indiana University School of Medicine, are doing this study to
better understand how the effects of certain medications are altered when taken
simultaneously, or in combination with each other. We will also look at how each volunteer's
genes (DNA) may affect the way these medications are metabolized.
We will test the hypothesis that the extent of drug-drug interaction caused by the
combination of erythromycin and diltiazem is not predictable from the extent of interaction
produced by each inhibitor alone. Specifically we will test the hypothesis that the
combination of erythromycin and diltiazem will cause a greater decrease in midazolam
intravenous and oral clearance than the sum of the decreases caused by each inhibitor alone.
Official title: The Effect of Concomitant Administration of Erythromycin and Diltiazem on CYP3A Activity in Healthy Volunteers
Study design: Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Pharmacokinetics Study
Primary Aims: To quantify the extent of the drug-drug interaction between erythromycin and midazolam
To quantify the extent of the drug-drug interaction between diltiazem and midazolam
To quantify the extent of the drug-drug interaction between the combination of diltiazem and erythromycin, and midazolam
Secondary Aims: To quantify the effects of erythromycin, diltiazem, and the combination of erythromycin and diltiazem on the electrocardiogram (EKG) PR interval
To quantify the effects of erythromycin, diltiazem, and the combination of erythromycin and diltiazem on the heart-rate corrected QT interval of the EKG
Many drugs such as diltiazem are metabolized by CYP3A4, the cytochrome P450 enzyme
responsible for the metabolism of erythromycin and when given together, the possibility
exists that one drug inhibits the metabolism of the other leading to an increase in plasma
concentration. The magnitude of this interaction is not known. It is therefore important to
define this effect because diltiazem is a drug that is used commonly to treat hypertension,
angina and atrial fibrillation and these patients may be given erythromycin for the treatment
of intercurrent bacterial infections.
Minimum age: 18 Years.
Maximum age: 50 Years.
Approximately 45 healthy volunteers may be recruited to participate in the study, with a
goal of 15 healthy volunteers (7 or 8 males) completing the entire four phases. All
1. Must be a non-smoker
2. Between 18 to 50 years of age
3. Have a body mass index of 30 or less
4. Must be willing to undergo a screening physical examination and proven to be free from
metabolic, cardiac, pulmonary, renal or hepatic dysfunction as determined by the
screening physical, medical history, 12-lead electrocardiography, and laboratory
values which include: a CMP (complete metabolic profile), a CBC/diff/plt (complete
blood count with differential and platelet count), serum pregnancy test (if
applicable), and UA (urinalysis). Also, given the uncertain effects of these drugs on
the fetus and the fact that hormonal contraceptives are prohibited, the female
subjects should be on two other forms of birth control (e. g. condom, contraceptive
Potential volunteers will be excluded:
1. If they have allergies or are hypersensitive to any of the study medications:
A. Midazolam (Versed) or related benzodiazepines drugs such as diazepam (Valium) or
B. Diltiazem (Cardizem, Dilacor) or related calcium channel blockers such as
verapamil (Calan, Isoptin).
C. Erythromycin (Erythrocin, E-mycin, Ery-tab) or related antibiotics such as
clarithromycin (Biaxin) or have experienced abdominal pain when taking erythromycin or
other related medications.
2. If they are taking any prescription medication on a regular basis including
contraceptives such as oral birth control pills, transdermal patches or injections
3. If they are taking over-the-counter medications, any herbal or dietary supplement
(including Benadryl, Sudafed, St. John's wort, herbal teas, vitamins and garlic
supplements) that cannot be stopped for the study duration. Use of over-the-counter
drugs for the treatment of minor, short-lived (2 to 3 days) symptoms may be allowable
(such as Tylenol) but must first be approved by a study investigator.
4. If they have donated blood within the past two months, or are anemic (have a
hemoglobin level less than 12. 5 mg/dl).
5. If they weigh less than 52 kg, or have a BMI (Body Mass Index) greater than 32.
6. If they have a screening or baseline EKG reading that is abnormal or could place them
at higher risk as decided by the study doctors (baseline corrected QT interval in the
EKG of 450 msec or greater or a baseline PR interval in the EKG of 210 msec or
7. If they have a history of bradycardia or consistently have a heart rate less than 55
beats per minutes.
8. If they have any history of heart disease or have a family medical history of sudden
death (heart stopping suddenly without warning).
9. If they have a history of psychiatric problems that may be exacerbated by
participation in this study, or if the subject can not state a good understanding of
this study's risks and requirements.
10. If they have a positive serum pregnancy test during the screening process or have a
positive urine pregnancy test (UPT) which will be obtained just prior to each of the
four study phases.
11. If they are currently breastfeeding.
12. If they have participated in any other study in which they have taken a research
medication within the past three months.
13. If they have a history of alcohol or drug abuse, or have used tobacco or marijuana
within the past three months.
14. If they are unwilling or unable to refrain from using drugs, alcohol, or any food
listed on the exclusion list below during this study.
15. If they are an employee or student under the supervision of any study investigator.
16. If they are unwilling or unable to follow the study rules.
Locations and Contacts
Indiana University Medical Center / GCRC, Indianapolis, Indiana 46202, United States
Starting date: April 2006
Ending date: December 2007
Last updated: December 12, 2007