title: Modelling the cardiovascular effects of ephedrine.
abstract: OBJECTIVE
  Recent reports have called into question the safety of ephedra supplements especially with regards to their cardiovascular effects. The purpose of this analysis was to characterize, via pharmacokinetic/pharmacodynamic modelling, the cardiovascular effects of ephedrine, the main active ingredient of ephedra, in apparently healthy, overweight volunteers.
  
  
  METHODS
  In a randomized, double-blind, crossover, placebo-controlled study, eight subjects received either placebo, 0.25, 0.5 or 1.0 mg kg(-1) ephedrine sulphate by mouth with a 7-day washout between treatments. Plasma ephedrine concentrations, heart rate and blood pressure were determined for 8 h postdose.
  
  
  RESULTS
  The pharmacokinetics of ephedrine were best described by a one-compartment model with first-order absorption and elimination. The percentage change in heart rate was described by a linear model with a resulting slope of 0.14%.l microg(-1) (CV = 59%). The percentage change in systolic blood pressure demonstrated clockwise hysteresis, and a sigmoidal tolerance model was used to describe the data. The mean maximum predicted effect (Emax) was 53.7% (CV = 41%) with an EC50 of 107 microg.l(-1) (CV = 65%) and an inhibitory maximum (Imax) of 39.8% (CV = 60%). Tolerance developed with a mean half-life of 15 min (range 6-140 min).
  
  
  CONCLUSIONS
  This is the first study to apply a comprehensive pharmacokinetic/pharmacodynamic model to the cardiovascular effects of orally administered ephedrine. Although systolic blood pressure increases quickly after administration, the increase is nearly abolished by compensatory mechanisms.
authors.affiliation: Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA. apersky@nc.rr.com
authors.forename: Adam M
authors.initials: AM
authors.lastname: Persky
authors.forename: N Seth
authors.initials: NS
authors.lastname: Berry
authors.forename: Gary M
authors.initials: GM
authors.lastname: Pollack
authors.forename: Kim L R
authors.initials: KL
authors.lastname: Brouwer
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004809:Ephedrine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D013566:Sympathomimetics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D013566:Sympathomimetics; D004809:Ephedrine