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.