Schütz E, Ha H R, Bühler F R, Follath F
J Cardiovasc Pharmacol. 1982;4 Suppl 3:S346-9.
Serum concentrations of verapamil and its main metabolite norverapamil as measured by high-pressure liquid chromatography were compared with blood pressure responses to long-term antihypertensive therapy with a slow-release formulation of verapamil (120-240 mg b.d.) in 14 patients with essential hypertension. Trough and peak verapamil concentrations varied widely, but in individual patients relatively stable drug levels were maintained up to 8 h after a morning dose. Even at 24 h verapamil concentrations greater than 50 ng/ml were present in 11 of 14 cases. Norverapamil concentrations were higher than those of the parent drug throughout the entire dosage interval. Blood pressure reduction less than or equal to 160/95 mm Hg was achieved in 13 patients by verapamil alone, but a direct relationship between drug levels and antihypertensive effects or the patient's age was not demonstrable. Despite a marked decrease of verapamil concentrations, blood pressure reduction persisted up to 24 h after the last dose. Thus, after repetitive dosing of slow-release verapamil, adequate blood pressure control is achieved by giving the drug twice (or perhaps once) daily.
采用高压液相色谱法测定了14例原发性高血压患者血清中维拉帕米及其主要代谢产物去甲维拉帕米的浓度，并将其与服用维拉帕米缓释制剂（每日两次，每次120 - 240 mg）进行长期抗高血压治疗后的血压反应进行了比较。维拉帕米的谷浓度和峰浓度差异很大，但在个体患者中，早晨服药后长达8小时可维持相对稳定的药物水平。即使在24小时时，14例中有11例的维拉帕米浓度仍大于50 ng/ml。在整个给药间隔期间，去甲维拉帕米的浓度均高于母体药物。仅使用维拉帕米治疗，13例患者的血压降低至160/95 mmHg或更低，但未发现药物水平与降压效果或患者年龄之间存在直接关系。尽管维拉帕米浓度显著下降，但在最后一剂后长达24小时血压仍持续降低。因此，重复服用维拉帕米缓释制剂后，每日给药两次（或可能一次）即可实现充分的血压控制。
