Persky Adam M, Berry N Seth, Pollack Gary M, Brouwer Kim L R
Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
Br J Clin Pharmacol. 2004 May;57(5):552-62. doi: 10.1111/j.1365-2125.2003.02062.x.
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.
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.
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).
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.
近期报告对麻黄补充剂的安全性提出质疑，尤其是其对心血管的影响。本分析的目的是通过药代动力学/药效学建模，在明显健康的超重志愿者中表征麻黄的主要活性成分麻黄碱对心血管的影响。
在一项随机、双盲、交叉、安慰剂对照研究中，8名受试者分别接受安慰剂、0.25、0.5或1.0mg·kg⁻¹硫酸麻黄碱口服，各治疗之间有7天的洗脱期。给药后8小时测定血浆麻黄碱浓度、心率和血压。
麻黄碱的药代动力学最好用具有一级吸收和消除的单室模型来描述。心率的百分比变化用线性模型描述，斜率为0.14%·μg⁻¹（CV = 59%）。收缩压的百分比变化呈现顺时针滞后现象，用S形耐受模型来描述数据。平均最大预测效应（Emax）为53.7%（CV = 41%），半数有效浓度（EC50）为107μg·L⁻¹（CV = 65%），最大抑制率（Imax）为39.8%（CV = 60%）。耐受性发展的平均半衰期为15分钟（范围6 - 140分钟）。
这是第一项将综合药代动力学/药效学模型应用于口服麻黄碱心血管效应的研究。尽管给药后收缩压迅速升高，但这种升高几乎被代偿机制消除。
