Molinaro M, Regazzi M B, Raffaghello S, Buggia I, Iacona I, Graziani P, Specchia G, Melzi D'eril G
Department of Pharmacology, IRCCS, Policlinico S. Matteo, Pavia, Italy.
J Clin Pharm Ther. 1994 Apr;19(2):111-5. doi: 10.1111/j.1365-2710.1994.tb01121.x.
The bioequivalence of a 600-mg methocel tablet containing buflomedil hydrochloride in sustained-release form was determined relative to a 300-mg CAP/carbovax-coated tablet of buflomedil hydrochloride in immediate-release form. The tablets were given to 20 patients in a double-blind placebo-controlled clinical study with cross-over between the administration plans. The 300-mg tablets were given b.i.d., at 8 a.m. and 8 p.m. while the 600-mg tablets were taken once a day at 8 a.m. (+placebo at 8 p.m.). Plasma samples were collected at appropriate times up to 24 h after administration and were analyzed for buflomedil with a validated high-performance liquid chromatographic procedure. Results showed an overall significant mean difference in absorption rate between the two formulations. The mean tmax (5.5 +/- 3.5 h) for the 600-mg tablet was longer (P < 0.001) than the tmax value (1.8 +/- 0.8 h) seen after administration of the first 300-mg tablet. Analysis of AUC(O-infinity) values indicated that the sustained-release preparation (32.1 +/- 20.7 micrograms/ml h) was not significantly different from the 300-mg tablet b.i.d. (28.7 +/- 16.0 micrograms/ml h). Furthermore, it was seen that single administration of a 600-mg sustained-release tablet of buflomedil hydrochloride delivered the same amount of total drug as a 300-mg tablet given twice a day.
测定了含盐酸丁咯地尔缓释制剂的600毫克甲基纤维素片相对于含盐酸丁咯地尔速释制剂的300毫克CAP/卡波普克斯包衣片的生物等效性。在一项双盲安慰剂对照临床研究中，将这些片剂给予20名患者，给药方案之间采用交叉设计。300毫克片剂每天两次，于上午8点和晚上8点服用，而600毫克片剂每天一次，于上午8点服用（晚上8点服用安慰剂）。在给药后长达24小时的适当时间采集血浆样本，并用经过验证的高效液相色谱法分析丁咯地尔。结果显示两种制剂之间的吸收速率总体存在显著平均差异。600毫克片剂的平均达峰时间（5.5±3.5小时）比首次服用300毫克片剂后的达峰时间值（1.8±0.8小时）更长（P<0.001）。对AUC（0-无穷大）值的分析表明，缓释制剂（32.1±20.7微克/毫升·小时）与300毫克片剂每日两次给药（28.7±16.0微克/毫升·小时）无显著差异。此外，还发现单次服用600毫克盐酸丁咯地尔缓释片与每日两次服用300毫克片剂的总给药量相同。
