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考察８名汉族男性健康志愿者口服８０ｍｇ和静滴５ｍｇ外消旋维拉帕米的心血管效应（心率、血压和ＰＲ间期），并结合对映体药代动力学分析其药效学特性。以三甲基－β－环糊精为手性选择剂，毛细管电泳法测定维拉帕米对映体血浆浓度。用药代动力学－药效学结合模型，即二房室模型加效应室，估算以维拉帕米总浓度和Ｓ－（－）－维拉帕米浓度对ＰＲ间期延长百分率的药效学参数。口服给药时，以维拉帕米总浓度估算的药效学参数Ｅｍａｘ（％），ＣＥ５０（μｇ·Ｌ－１），Ｋｅｏ和γ分别为４３．７±２１．１，６９．４±３０．３，３．６４±４．７和２．８５±２．０１；以Ｓ－（－）－维拉帕米估算的药效学参数分别为４７．７±２６．９，１４．３±８．５，５．２３±５．５和３．２４±１．８。静脉给药时，以维拉帕米总浓度估算的药效学参数分别为３５．２±１３．３，２９．７±１２．９，６．３６±３．２和２．２８±１．６；以Ｓ－（－）－维拉帕米估算的药效学参数分别为３５．７±１７．２，１３．４±８．４１，７．１３±３．４２和２．５２±１．５２。因此，在不同给药途径下或对映体比率的个体间差异较大时，以Ｓ－（－）－维拉帕米浓度与效应拟合药效学参数，较总浓度更有临床意义。
The cardiovascular effects (heart rate, blood pressure and PR interval) of oral administration of 80 mg and intravenous infusion of 5 mg racemic verapamil in 8 Han male volunteers were investigated and their pharmacodynamic properties were analyzed in combination with enantiomer pharmacokinetics . The enantiomeric plasma concentrations of verapamil were determined by capillary electrophoresis with trimethyl-β-cyclodextrin as chiral selector. A pharmacokinetic-pharmacodynamic model, a two-compartment model with an effect chamber, was used to estimate the pharmacodynamic parameters of the verapamil total concentration and the S - (-) - verapamil concentration for the percentage of prolongation of the PR interval . At oral administration, the pharmacodynamic parameters Emax (%), CE50 (μg · L-1), Keo and γ estimated at the total concentration of verapamil were 43.7 ± 21.1 and 69.4 ± 30 .3, 3.64 ± 4.7 and 2.85 ± 2.01, respectively. The pharmacodynamic parameters estimated by S - (-) - verapamil were 47.7 ± 26.9 and 14.3 ± 8.5, 5.23 ± 5.5 and 3.24 ± 1.8. Pharmacodynamic parameters estimated at the total verapamil concentration of 35.2 ± 13.3, 29.7 ± 12.9, 6.36 ± 3.2 and 2.28 ± 1, respectively, for intravenous administration. 6; the pharmacodynamic parameters estimated with S - (-) - verapamil were 35.7 ± 17.2, 13.4 ± 8.41, 7.13 ± 3.42 and 2.52 ± 1 .52. Therefore, the pharmacodynamic parameters fitted by S - (-) - verapamil concentration and effect were more significant than the total concentration when there were significant differences between individuals under different routes of administration or enantiomeric ratios.