Drug Interaction Study of Tegretol (Carbamazepine) and St. John's Wort in Normal Volunteers

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00006395
First received: October 7, 2000
Last updated: March 3, 2008
Last verified: September 2000
  Purpose

St. John's Wort is a popular dietary supplement that many patients-including those with epilepsy or seizures-take in addition to their regular medicines to elevate mood or relieve stress. Preliminary research indicates that this supplement can speed the metabolism of the anti-seizure drug Tegretol, causing reduced blood levels of the drug. Patients who take Tegretol to control their seizures may have more frequent seizures if the blood level of the drug drops too low. A recent study shows that this effect is not seen when Tegretol is taken for at least 3 weeks. The present study will examine whether there is a medically important drug interaction between St. John's wort and Tegretol when Tegretol is taken for 1 day.

Normal healthy volunteers between 21 and 65 years old who are not taking medicines that can affect the metabolism of drugs in the liver and have not used St. John's wort for at least 30 days may be eligible for this 25-day study.

Participants will take a 400-mg dose of Tegretol after fasting overnight. Blood samples will be drawn the next day during a 12-hour clinic stay at the following intervals: just before the Tegretol dose and at 1, 2, 4, 6, 8, 10, 24, 34, 48 and 72 hours after the dose. A catheter will be placed in the vein to prevent the need for multiple needle sticks until after the 10-hour sample. After completing the blood sampling, participants will take 300 mg of St. John's wort 3 times a day with meals for 2 weeks. After 2 weeks, another fasting dose of Tegretol will be given and the 72-hour blood study will be repeated.

This study may provide information important for the care of patients with epilepsy who take both Tegretol and St. John's Wort.


Condition Intervention Phase
Healthy
Drug: St. John's Wort
Phase 4

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Evaluation of the Effect of St. John's Wort on Single Dose Carbamazepine Pharmacokinetics in Normal Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 12
Study Start Date: October 2000
Estimated Study Completion Date: April 2001
Detailed Description:

Alternative or complementary therapies are widely used by patients with epilepsy. St. John's Wort is one of the most popular herbal dietary supplements with a variety of claims including mood elevation and stabilization, stress relief, anti-viral effects, and enhancement of the immune system. We have previously demonstrated that treatment with St. John's Wort for 14 days does not induce the clearance of carbamazepine under steady state conditions of autoinduction of carbamazepine clearance. One proposed mechanism for this lack of effect is that St. John's Wort is not sufficiently potent to further induce previously induced CYP3A4 enzyme activity. The purpose of this study is to investigate the effect of St. John's Wort on single dose carbamazepine pharmacokinetics under conditions of uninduced CYP3A4. To evaluate this potential drug interaction, as well as the effect of St. John's Wort on epoxide hydrolase activity, eight normal healthy subjects will be enrolled into this pharmacokinetic study. Subjects will take a single 400 mg dose of carbamazepine followed by serial blood sampling over 72 hours for carbamazepine and carbamazepine epoxide plasma concentrations. Subjects will then begin taking a standardized formulation of St. John's Wort three times daily with meals for two weeks. Following 2 weeks of St. John's Wort subjects will then again take a single 400 mg dose of carbamazepine and have serial blood samples collected for carbamazepine and carbamazepine epoxide plasma concentrations. The total carbamazepine and carbamazepine epoxide exposure (AUC), oral clearance (CL/F), and maximal concentrations (Cmax) will be compared between treatment phases to characterize the potential drug interaction.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Male or female.

Healthy by medical history and physical exam.

Age between 21 and 65 years old.

Non-smoker for a minimum of 6 months.

AST/SGOT less than or equal to 2 x upper limit of normal.

Serum creatinine less than or equal to upper limit of normal.

Hemoglobin greater than or equal to 10 g/dl.

Females of childbearing potential must be using a reliable form of birth control other than hormonal contraceptives.

No concomitant therapy with other inhibitors or inducers of cytochrome P-450 mediated drug metabolism within 30 days of study.

No inability to remain free of chronic medications and alcohol for at least 2 weeks prior to and during the study.

No previous use of St. John's Wort. Subjects with prior history of St. John's Wort use must abstain from use for 30 days prior to study participation.

No presence of renal, hepatic, cardiovascular, hematologic, neurologic, psychiatric, or respiratory disease or any other condition that may interfere with the interpretation of the study results or not be in the best interests of the subject in the opinion of the investigator.

No positive urine pregnancy test.

No presence of persistent diarrhea or malabsorption that would interfere with the patients ability to adequately absorb drugs.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006395

Locations
United States, Maryland
Warren G. Magnuson Clinical Center (CC)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00006395     History of Changes
Other Study ID Numbers: 010005, 01-CC-0005
Study First Received: October 7, 2000
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Antiepileptic
CYP3A4
Herbal
Induction
Interaction

Additional relevant MeSH terms:
Carbamazepine
Analgesics
Analgesics, Non-Narcotic
Anticonvulsants
Antimanic Agents
Central Nervous System Agents
Central Nervous System Depressants
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 22, 2014