Document Detail

Enhanced stimulant and metabolic effects of combined ephedrine and caffeine.
MedLine Citation:
PMID:  15060505     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Herbal weight loss and athletic performance-enhancing supplements that contain ephedrine and caffeine have been associated with serious adverse health events. We sought to determine whether ephedrine and caffeine have clinically significant pharmacologic interactions that explain these toxicities. METHODS: Sixteen healthy adults ingested 25 mg ephedrine, 200 mg caffeine, or both drugs in a randomized, double-blind, placebo-controlled crossover study. Plasma and urine samples were collected over a 24-hour period and analyzed by liquid chromatography-tandem mass spectrometry for ephedrine and caffeine concentrations. Heart rate, blood pressure, and subjective responses were recorded. Serum hormonal and metabolic markers were serially measured during a 3-hour fasting period. RESULTS: Ephedrine plus caffeine increased systolic blood pressure (peak difference, 11.7 +/- 9.4 mm Hg; compared with placebo, P =.0005) and heart rate (peak difference, 5.9 +/- 8.8 beats/min; compared with placebo, P =.001) and raised fasting glucose, insulin, free fatty acid, and lactate concentrations. Ephedrine alone increased heart rate and glucose and insulin concentrations but did not affect systolic blood pressure. Caffeine increased systolic blood pressure and plasma free fatty acid and urinary epinephrine concentrations but did not increase heart rate. Compared with ephedrine, caffeine produced more subjective stimulant effects. Clinically significant pharmacokinetic interactions between ephedrine and caffeine were not observed. Women taking oral contraceptives had prolonged caffeine elimination (mean elimination half-life, 9.7 hours versus 5.0 hours in men; P =.05), but sex differences in pharmacodynamic responses were not seen. CONCLUSIONS: The individual effects of ephedrine and caffeine were modest, but the drugs in combination produced significant cardiovascular, metabolic, and hormonal responses. These enhanced effects appear to be a result of pharmacodynamic rather than pharmacokinetic interactions.
Christine A Haller; Peyton Jacob; Neal L Benowitz
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  75     ISSN:  0009-9236     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-04-02     Completed Date:  2004-05-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  259-73     Citation Subset:  AIM; IM    
Department of Medicine, Division of Clinical Pharmacology, University of California, San Francisco, CA 94143, USA.
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MeSH Terms
Area Under Curve
Biological Availability
Blood Pressure / drug effects
Caffeine / administration & dosage*,  pharmacokinetics*
Cardiovascular System / drug effects*
Central Nervous System Stimulants / administration & dosage,  adverse effects*,  pharmacokinetics
Confidence Intervals
Cross-Over Studies
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Drug Interactions
Ephedrine / administration & dosage*,  pharmacokinetics*
Heart Rate / drug effects
Hemodynamics / drug effects
Middle Aged
Risk Assessment
Sensitivity and Specificity
Grant Support
Reg. No./Substance:
0/Central Nervous System Stimulants; 299-42-3/Ephedrine; 58-08-2/Caffeine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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