Fuenmayor N T, Faggin B M, Cubeddu L X
Perez Carreno Hospital, IVSS, Division of Nephrology, Caracas, Venezuela.
Drugs. 1992;44 Suppl 1:1-11. doi: 10.2165/00003495-199200441-00002.
The antihypertensive effects of the regular immediate release formulation of verapamil (verapamil IR) and the newer sustained release formulation of verapamil (verapamil SR) were compared in Hispanic patients with untreated essential hypertension. Verapamil IR was given in 3 divided doses (80 or 160mg 3 times daily) and verapamil SR was given either as a single daily dose of 240mg or as 240mg every 12 hours. With both formulations there was a significant reduction in systolic (SBP) and diastolic blood pressure (DBP); a greater lowering of BP was observed with verapamil 480 mg/day than with 240 mg/day. With verapamil SR 480 mg/day, 91% of patients had reductions in SBP and DBP greater than 20 and 15mm Hg, respectively. In addition, 83% of patients reached normotension. With the lower dose (240mg once daily), 83% of patients had decreases in DBP greater than 10mm Hg and 73% of patients achieved normotension. Comparable effects were achieved with verapamil IR. With verapamil IR there was a more rapid fall in BP which peaked 3 to 4 hours postdose, whereas with verapamil SR a more gradual and sustained BP reduction was observed. Only small changes in heart rate (HR) were observed with verapamil IR and verapamil SR. For verapamil SR, the mean increase in HR was 5 beats/min (to 80 beats/min) and the mean decrease in HR was 13 beats/min (to 62 beats/min). Both verapamil SR and verapamil IR prolonged the PR interval of the ECG. An equal degree of PR prolongation was observed with 240 and 480 mg/day. The incidence of side effects (headache, palpitations, dizziness and flushing) was dose dependent, decreased with continuous treatment and was much higher with verapamil IR than with verapamil SR. Steady-state plasma verapamil concentrations were monitored. Compared with verapamil IR, verapamil SR produced a more gradual rise and a more sustained elevation of plasma verapamil and norverapamil concentrations. Comparable trough verapamil concentrations (Cmin) were observed with verapamil IR (98 micrograms/L) and SR (81 micrograms/L); morning Cmin verapamil concentrations were higher than daytime Cmin values. The normalised area under the plasma concentration-time curve (AUC) and maximum concentration (Cmax) were 10 to 20% greater for verapamil IR than SR. The 2-fold increase in oral dose produced a 2.2- and 2.4-fold increase in AUC for verapamil IR and SR, respectively, associated with a 20% reduction in metabolism to norverapamil. Fasting increased the rate and extent of absorption of verapamil.(ABSTRACT TRUNCATED AT 400 WORDS)
在未接受治疗的西班牙裔原发性高血压患者中，比较了维拉帕米普通速释制剂（维拉帕米IR）和新型缓释制剂（维拉帕米SR）的降压效果。维拉帕米IR分3次给药（80或160mg，每日3次），维拉帕米SR每日单次给药240mg或每12小时给药240mg。两种制剂均可使收缩压（SBP）和舒张压（DBP）显著降低；与每日240mg的维拉帕米相比，每日480mg的维拉帕米降压效果更显著。每日480mg的维拉帕米SR治疗时，91%的患者SBP和DBP分别降低超过20和15mmHg。此外，83%的患者血压恢复正常。较低剂量（每日一次240mg）治疗时，83%的患者DBP降低超过10mmHg，73%的患者血压恢复正常。维拉帕米IR也有类似效果。维拉帕米IR使血压下降更快，给药后3至4小时达到峰值，而维拉帕米SR使血压下降更缓慢且持续时间更长。维拉帕米IR和维拉帕米SR治疗时，心率（HR）仅有微小变化。对于维拉帕米SR，HR平均增加5次/分钟（至80次/分钟），平均降低13次/分钟（至62次/分钟）。维拉帕米SR和维拉帕米IR均延长了心电图的PR间期。每日240mg和480mg时，PR间期延长程度相同。副作用（头痛、心悸、头晕和潮红）的发生率与剂量相关，持续治疗后降低，且维拉帕米IR的副作用发生率远高于维拉帕米SR。监测了稳态血浆维拉帕米浓度。与维拉帕米IR相比，维拉帕米SR使血浆维拉帕米和去甲维拉帕米浓度升高更缓慢且持续时间更长。维拉帕米IR（98μg/L）和SR（81μg/L）的谷浓度（Cmin）相当；早晨的Cmin维拉帕米浓度高于白天的Cmin值。维拉帕米IR的血浆浓度-时间曲线下归一化面积（AUC）和最大浓度（Cmax）比SR高10%至20%。口服剂量增加2倍时，维拉帕米IR和SR的AUC分别增加2.2倍和2.4倍，同时去甲维拉帕米代谢降低20%。空腹增加了维拉帕米的吸收速率和程度。（摘要截断于400字）
