Comparison of the acute pharmacodynamic responses after single doses of ephedrine or sibutramine in healthy, overweight volunteers.
OBJECTIVE
With an increase in the incidence of obesity, tremendous effort has been devoted to the development of weight loss agents and the prospective surrogate markers of both a product's efficacy and safety. The objective of the present study was to compare the pharmacodynamic responses of ephedrine and sibutramine using surrogate markers of weight loss potential and potential adverse events.


METHODS
The study was designed as a 5-way, randomized, double-blinded, placebo-controlled trial with 3 single doses of ephedrine sulfate (0.25, 0.5 and 1 mg x kg(-1)) followed by an open-labeled sibutramine (10 mg) treatment. Healthy, mildly overweight (BMI = 25) subjects were administered the respective treatment and pharmacokinetic and pharmacodynamic measurements (body surface temperature, resting metabolic rate, blood pressure, heart rate, glucose, glycerol, nonesterified fatty acids, triglycerides) were obtained for 8 hours post dose and for an additional 4 measurements during the sibutramine treatment period.


RESULTS
Sibutramine treatment significantly increased resting metabolic rate compared to the placebo condition. Ephedrine significantly increased heart rate, systolic blood pressure and glucose but did not significantly affect other measurements.


CONCLUSIONS
Both sibutramine and ephedrine have been shown to have weight loss potential, however, they elicit different metabolic and biochemical responses after a single dose. The nontherapeutic responses from these types of compounds may serve as a screening tool for the development of agents in the treatment of obesity.
Persky
A M
AM
Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
Ng
C
C
Song
M H
MH
Lancaster
M E
ME
Balderson
D E
DE
Paulik
M A
MA
Brouwer
K L R
KL
D000328:Adult; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D001481:Basal Metabolism / Q000187:drug effects*; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D001823:Body Composition; D015992:Body Mass Index; D003404:Creatinine / Q000097:blood; D003503:Cyclobutanes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004311:Double-Blind Method; D004809:Ephedrine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D005990:Glycerol / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D019440:Anti-Obesity Agents; D001786:Blood Glucose; D003503:Cyclobutanes; D014280:Triglycerides; D003404:Creatinine; D004809:Ephedrine; D005990:Glycerol; C058254:sibutramine