Sawicki Wiesław, Janicki Stanisław
Department of Pharmaceutical Technology, Medical University of Gdansk, ul. Hallera 107, 80-416, Gdáńsk, Poland.
Int J Pharm. 2002 May 15;238(1-2):181-9. doi: 10.1016/s0378-5173(02)00069-8.
Pharmacokinetics of verapamil and its metabolite norverapamil, from buccal drug formulation administered in a dose 20 mg in relation to conventional tablets of verapamil 40 mg, used in medical practice, was determined. Buccal formulation has previously been designed as an alternative form of dosing verapamil. Bioavailability was determined by a crossover method in 12 healthy volunteers. Drug concentration in plasma was determined by means of HPLC with a fluorescence detector. For buccal formulation the average values of C(max) and AUC(0-24 h) for verapamil were much higher than for the reference Staveran tablets and amounted to 51.28 and 320.23 ng/ml h, respectively. However, for norverapamil the corresponding values for buccal formulation were much lower than for a conventional tablet. It has been demonstrated that the proposed buccal verapamil dosing ensures different metabolism of the drug as compared to tablets. Better parameters of bioavailability of verapamil from buccal formulation of twice a smaller dose than that in the tablet, prove that this new drug might be form more effective clinically than the conventional one.
测定了与医学实践中使用的 40 毫克维拉帕米常规片剂相比，20 毫克剂量的颊部给药制剂中维拉帕米及其代谢产物去甲维拉帕米的药代动力学。颊部制剂先前已被设计为维拉帕米给药的替代形式。采用交叉试验法在 12 名健康志愿者中测定生物利用度。血浆中的药物浓度通过配备荧光检测器的高效液相色谱法测定。对于颊部制剂，维拉帕米的 C(max) 和 AUC(0 - 24 h) 平均值远高于参比制剂 Staveran 片剂，分别为 51.28 和 320.23 ng/ml·h。然而，对于去甲维拉帕米，颊部制剂的相应值远低于常规片剂。已证明，与片剂相比，所提议的颊部维拉帕米给药方式可确保药物的不同代谢。与片剂相比，颊部制剂中剂量减半的维拉帕米具有更好的生物利用度参数，证明这种新剂型在临床上可能比传统剂型更有效。
