title: Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use.
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.
authors.affiliation: Division of Clinical Pharmacology, San Francisco General Hospital, University of California, 94143, USA. dchaller@worldnet.att.net
authors.forename: Christine A
authors.initials: CA
authors.lastname: Haller
authors.forename: Peyton
authors.initials: P
authors.lastname: Jacob
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D002110:Caffeine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D000697:Central Nervous System Stimulants / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004644:Emotions / Q000187:drug effects; D029789:Ephedra / Q000378:metabolism*; D029790:Ephedra sinica; D004809:Ephedrine / Q000097:blood; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D010665:Phenylpropanolamine / Q000097:blood; D010865:Pilot Projects; D012016:Reference Values; D013805:Theobromine / Q000493:pharmacokinetics; D013806:Theophylline / Q000493:pharmacokinetics
chemical_list: D000697:Central Nervous System Stimulants; C092099:guarana powder; C005331:norpseudoephedrine; D010665:Phenylpropanolamine; D002110:Caffeine; D013806:Theophylline; D004809:Ephedrine; D013805:Theobromine