Pharmacokinetics and Drug Disposition
Clinical Pharmacology & Therapeutics (2002) 71, 421–432; doi: 10.1067/mcp.2002.124523
Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use*
Christine A. Haller MD1, Peyton Jacob III PhD1 and Neal L. Benowitz MD1
1Division of Clinical Pharmacology, San Francisco General Hospital, University of California, San Francisco.
Correspondence: Christine A. Haller, MD, University of California, San Francisco, Division of Clinical Pharmacology, Box 1220, San Francisco, CA 94143. E-mail: dchaller@worldnet.att.net
*Supported by United States Public Health Service grants K23AT00069-01 (National Center for Complementary and Alternative Medicine), DAO2277, and DA012393 (National Institute on Drug Abuse) and by a General Clinical Research Center Award (5-MO1-RR-00083-39).
Received 24 January 2002; Accepted 12 March 2002.
Abstract
Objective: Serious cardiovascular toxicity has been reported in people taking dietary supplements that contain ma huang (Ephedra) and guarana (caffeine). We assessed the pharmacokinetics and pharmacodynamics of a dietary supplement that contains these herbal stimulants.
Methods: Eight healthy adults received a single oral dose of a thermogenic dietary supplement labeled to contain 20 mg ephedrine alkaloids and 200 mg caffeine after an overnight fast. Serial plasma and urine samples were analyzed by use of liquid chromatography-tandem mass spectrometry for ephedrine alkaloid and caffeine concentrations, and heart rate and blood pressure were monitored for 14 hours.
Results: Plasma clearance and elimination half-lives for ephedrine, pseudoephedrine, and caffeine were comparable to published values reported for drug formulations. A prolonged half-life of ephedrine and pseudoephedrine was observed in 1 subject with the highest urine pH. Mean systolic blood pressure increased significantly to a maximum of 14 mm Hg above baseline at 90 minutes after ingestion (P < .001). There was a lag in the mean heart rate response that reached a maximum change of 15 beats/min above baseline at 6 hours after ingestion (P < .001). Diastolic blood pressure changes were insignificant. Two subjects who were taking oral contraceptives had longer caffeine half-lives (15.5 
0.3 hours versus 5.6 1.7 hours) and lower values for oral clearance (0.34 0.01 mL/min 
kg versus 0.99 0.41 mL/min kg) than subjects who were not taking oral contraceptives.
Conclusions: Botanical stimulants have disposition characteristics similar to their pharmaceutical counterparts, and they can produce significant cardiovascular responses after a single dose.
