Article date: May 2004
By: Adam M. Persky, N. Seth Berry, Gary M. Pollack, Kim L. R. Brouwer, in Volume 57, Issue 5, pages 552-562
Aims 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 µg−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 µg·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.
DOI: 10.1111/j.1365-2125.2003.02062.x
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