Mattila J, Mäntylä R, Taskinen J, Männistö P
Eur J Drug Metab Pharmacokinet. 1985 Apr-Jun;10(2):133-8. doi: 10.1007/BF03189707.
Pharmacokinetics of conventional 80 mg tablets and two types of sustained-release (SR) tablets containing 120 and 200 mg of verapamil were compared cross-over in 12 healthy volunteers. Serum concentrations of verapamil and norverapamil were analyzed both after a single oral dose and at steady state after t.i.d. administration of conventional tablets and b.i.d. administration of SR tablets. After 120 mg SR tablets serum concentrations of verapamil usually remained below 100 ng/ml for 5 days. This inadequate bioavailability was caused by very slow absorption. The relative bioavailability of verapamil in 200 mg SR tablets was 93-96% as compared to the conventional tablets. After 200 mg X 2 and 80 mg X 3, the peak serum levels were about 300 and 190 ng/ml, respectively and the trough levels 123-153 and 52-56 ng/ml, respectively. The verapamil/norverapamil ratio varied from 0.69 to 0.84 after a single dose and from 0.8 to 0.93 at steady-state. By the 4th days of treatment, the accumulation ratios ranged between 1.75-2.07 and 1.30-1.75 for verapamil and norverapamil, respectively. For each preparation studied, the apparent Cltot of verapamil was significantly reduced at steady-state. These results show that 200 mg SR verapamil tablets fulfill the basic requirements of retard preparations allowing for twice or even once daily administration.
在12名健康志愿者中进行交叉试验，比较了常规80毫克片剂以及两种分别含有120毫克和200毫克维拉帕米的缓释（SR）片剂的药代动力学。在单次口服给药后以及在常规片剂每日三次给药和SR片剂每日两次给药达到稳态后，分析了维拉帕米和去甲维拉帕米的血清浓度。服用120毫克SR片剂后，维拉帕米的血清浓度通常在5天内保持低于100纳克/毫升。这种生物利用度不足是由吸收非常缓慢导致的。与常规片剂相比，200毫克SR片剂中维拉帕米的相对生物利用度为93 - 96%。服用200毫克×2片和80毫克×3片后，血清峰值水平分别约为300纳克/毫升和190纳克/毫升，谷值水平分别为123 - 153纳克/毫升和52 - 56纳克/毫升。单次给药后维拉帕米/去甲维拉帕米的比值在0.69至0.84之间，稳态时在0.8至0.93之间。到治疗第4天时，维拉帕米和去甲维拉帕米的蓄积比分别在1.75 - 2.07和1.30 - 1.75之间。对于所研究的每种制剂，维拉帕米的表观总清除率在稳态时均显著降低。这些结果表明，200毫克SR维拉帕米片剂满足缓释制剂的基本要求，允许每日给药两次甚至一次。
