Follath F, Ha H R, Schütz E, Bühler F
Br J Clin Pharmacol. 1986;21 Suppl 2(Suppl 2):149S-153S. doi: 10.1111/j.1365-2125.1986.tb02864.x.
Verapamil is a racemic mixture of two optical isomers, the (-)-form being the more active component. Recent studies indicate a rapid hepatic transformation of (-)-verapamil, which results in different concentration-effect relationships after oral and intravenous administration. In practice the important pharmacokinetic properties of verapamil are low bioavailability (20%), predominant elimination by metabolism (greater than 95%) and a relatively short half-life (t1/2, beta is 3-5 h). After repeated dosing, the rate of hepatic drug clearance seems to decrease. Slow release (SR) formulations of verapamil may offer certain therapeutic advantages during long-term treatment. A comparison of conventional (C) and SR tablets in a 1-week treatment of eight cardiac patients showed a relative bioavailability (AUCSR/AUCC) of 90 +/- 30%. More stable serum drug levels were maintained by 12-hourly administration of SR verapamil. A further study using a new 240 mg SR preparation in patients with arterial hypertension showed that even a single daily dose can be sufficient for adequate blood pressure control over 24 h.
维拉帕米是两种旋光异构体的外消旋混合物，(-)-型是活性更强的成分。最近的研究表明，(-)-维拉帕米在肝脏中迅速转化，这导致口服和静脉给药后浓度-效应关系有所不同。实际上，维拉帕米重要的药代动力学特性包括生物利用度低（20%）、主要通过代谢消除（超过95%）以及半衰期相对较短（t1/2，β为3 - 5小时）。重复给药后，肝脏药物清除率似乎会降低。维拉帕米缓释（SR）制剂在长期治疗期间可能具有一定的治疗优势。对8名心脏病患者进行为期1周的常规（C）片剂和SR片剂比较，结果显示相对生物利用度（AUCSR/AUCC）为90±30%。每12小时服用一次SR维拉帕米可维持更稳定的血清药物水平。另一项针对动脉高血压患者使用新型240毫克SR制剂的研究表明，即使每日单次给药也足以在24小时内充分控制血压。
