Pharmacology of ephedra alkaloids and caffeine after single‐dose dietary supplement use

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. Clinical Pharmacology & Therapeutics (2002) 71 , 421–432; doi: 10.1067/mcp.2002.124523