Popović J, Mitić R, Sabo A, Mikov M, Jakovljević V, Daković-Svajcer K
Faculty of Medicine, Pharmacology Department, Novi Sad, Serbia.
Eur J Drug Metab Pharmacokinet. 2006 Apr-Jun;31(2):87-96. doi: 10.1007/BF03191124.
The pharmacokinetics of a new verapamil retard tablet formulation have been investigated in a randomized cross-over bioequivalence study on 12 healthy subjects. The drug was given orally at a single new or standard retard tablet dose of 240mg and at a single intravenous dose of 5mg. Plasma verapamil concentrations were determined by HPLC. New retard tablets produced peak plasma verapamil concentrations of 81.34+/-5.69microg/l, time to peak plasma concentrations of 4.91+/-0.89h and an AUC (0-24h) of 1291+/-103.4h x microg/l, with a terminal phase half-life of 55.1+/-14.9h. After intravenous administration verapamil exhibited biphasic elimination kinetics with a terminal plasma half-life of 2.36+/-0.42h and systemic clearance of 34.32+/-5.81 l/h. Bioavailability of the new peroral retard formulation ranged from 19.49+/-4.41% to 67.69+/-11.70%. Absorption rates and amounts were evaluated by means of the spline-convolutional method. Input rates for the new verapamil retard formulation ranged from 0.77+/-0.20mg/h to 5.57+/-1.58mg/h. The cumulative amount of verapamil input was 39.17+/-9.71% for the new retard tablets. All pharmacokinetic parameters for the new verapamil retard tablet formulation, were in reasonable agreement with the data obtained on already registered verapamil retard formulations, indicating their bioequivalence.
在一项针对12名健康受试者的随机交叉生物等效性研究中，对一种新的维拉帕米缓释片制剂的药代动力学进行了研究。以240mg的单一新缓释片或标准缓释片剂量以及5mg的单一静脉剂量口服给药。通过高效液相色谱法测定血浆维拉帕米浓度。新的缓释片产生的血浆维拉帕米峰值浓度为81.34±5.69μg/l，达血浆峰值浓度的时间为4.91±0.89小时，AUC（0 - 24小时）为1291±103.4小时×μg/l，终末相半衰期为55.1±14.9小时。静脉给药后，维拉帕米呈现双相消除动力学，终末血浆半衰期为2.36±0.42小时，全身清除率为34.32±5.81 l/h。新的口服缓释制剂的生物利用度范围为19.49±4.41%至67.69±11.70%。通过样条卷积法评估吸收速率和吸收量。新的维拉帕米缓释制剂的输入速率范围为0.77±0.20mg/h至5.57±1.58mg/h。新缓释片的维拉帕米累计输入量为39.17±9.71%。新的维拉帕米缓释片制剂的所有药代动力学参数与已注册的维拉帕米缓释制剂所获得的数据合理一致，表明它们具有生物等效性。
