Effects of Kava on the Body's Elimination of Caffeine and Dextromethorphan
Avainsanat
Abstrakti
Kuvaus
Kava (piper methysticum) is a complementary or alternative medication used for purported anxiolytic and sedative effects. Despite its widespread use there is no data regarding potential for drug interactions or its effects on the electroencephalogram. The purpose of this study is to determine the effect of administration of kava for 3 weeks on the activity of cytochrome p450, 1A2, 2D6, 3A4; NAT2, and XO. Additionally, the effect of kava on EEG measured beta amplitude will be evaluated. Fifteen healthy volunteers will undergo enzyme activity phenotyping by ingesting 2 mg/kg of caffeine and 30 mg of dextromethorphan followed by an overnight urine collection. Following completion of two separate baseline evaluations, separated by 1 week, subjects will then take 1 capsule containing 60 mg of kavalactones three times daily for 3 weeks. Following 3 weeks of therapy subjects will undergo repeat enzyme activity phenotyping as described previously. Enzyme activity following 3 weeks of kava will be compared to pre-treatment values to characterize the magnitude of inhibition and/or induction of CYP1A2, CYP2D6, CYP3A4, NAT2, and XO activity. Additionally, subjects will have EEG testing performed to evaluate the effect of kava on beta amplitude. EEG's will be performed the day before the first baseline phenotyping procedure and then following three weeks of kava (the day before the final phenotyping procedure). Beta amplitude following three weeks of kava will be compared to pre-treatment values to evaluate the magnitude of pharmacodynamic effect. The results of this study will be used to facilitate the development of protocols to evaluate the magnitude of interactions between clinically relevant traditional medications and kava as well as studies to compare the pharmacologic effect of kava to the effects of benzodiazepines.
Päivämäärät
Viimeksi vahvistettu: | 12/31/2000 |
Ensimmäinen lähetys: | 01/26/2001 |
Arvioitu ilmoittautuminen lähetetty: | 12/08/2002 |
Ensimmäinen lähetetty: | 12/09/2002 |
Viimeisin päivitys lähetetty: | 03/02/2008 |
Viimeisin päivitys lähetetty: | 03/03/2008 |
Todellinen opintojen alkamispäivä: | 12/31/2000 |
Arvioitu tutkimuksen valmistumispäivä: | 03/31/2001 |
Ehto tai tauti
Interventio / hoito
Drug: kava (Piper methysticum)
Vaihe
Kelpoisuusehdot
Sukupuolet, jotka ovat kelpoisia tutkimukseen | All |
Hyväksyy terveelliset vapaaehtoiset | Joo |
Kriteeri | Male or female Healthy by medical history and physical exam Age greater than 21 years old No concurrent medications Non-smoker (for at least 6 months if prior history of smoking) Laboratory values within the following guidelines: AST/SGOT less than or equal 1.5 X ULN Bilirubin less than or equal 1.5 X ULN Serum creatinine less than or equal ULN Hemoglobin less than 10 g/dl Females of child bearing potential must be using a reliable form of birth control other than hormonal contraceptives Ability to abstain from caffeine containing foods/beverages, ethanol, grapefruit or grapefruit juice and charbroiled foods for 72 hours prior to, and the day of, phenotyping procedures. Normal EEG during baseline testing. No patients using concomitant therapy with other inhibitors or inducers of cytochrome P-450 mediated drug metabolism within 30 days of study. No patients with inability to remain free of chronic medications and alcohol for atleast 2 weeks prior to and during the study. 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. Positive urine pregnancy test. The presence of persistent diarrhea or malabsorption that would interfere with the patient's ability to adequately absorb drug. Drug or alcohol use that may impair safety or adherence. |