Murata Isamu, Arai Narutoshi, Fukushima Aishi, Saito Astuko, Inoue Yutaka, Kimura Masayuki, Kanamoto Ikuo
Laboratory of Drug Safety Management, Faculty of Pharmaceutical Science, Josai University.
Yakugaku Zasshi. 2015;135(9):1049-55. doi: 10.1248/yakushi.15-00005.
Cancer patients often report a decreased quality of life due to cancer-related pain, especially neuropathic pain, which is difficult to manage and often develops resistance to morphine. Thus a supplementary analgesic can play an important role in the treatment of cancer-related pain. Carbamazepine (CBZ), for example, can be effective, but only if the patient can take medication orally because it is limited to oral administration. In this study we investigated the efficacy of a suppository containing CBZ tablet in hospital preparations. We selected a base for the suppository of either polyethylene glycol (P), Witepsol VOSCO(®) H-15 (H), or Witepsol VOSCO(®) S-55 (S). Six to eight in vitro and in vivo groups were divided randomly based on route of administration and treatment: intravenous (i.v.), per os (p.o.), and intrarectal administration (i.r.) (composed of CBZ powder and tablet formulations, CBZp and CBZt) prepared in either a base of P, H, or S (CBZp/P, CBZp/H, CBZp/S, CBZt/P, CBZt/H, and CBZt/S). The hardness levels of the CBZt suppository group were significantly lower than the CBZp suppository group. The drug release profiles of the CBZt suppository group were high in order of P, H, and S; there were no significant differences between these groups and the CBZp suppository group. The maximum drug concentration time levels of the CBZt suppository group significantly increased compared with the p.o. group. These two groups had equivalent maximum drug concentration and bioavailability levels. These results suggest that a suppository containing CBZ tablet can be useful for hospital preparations.
癌症患者常因癌症相关疼痛,尤其是神经性疼痛而报告生活质量下降,这种疼痛难以控制,且常对吗啡产生耐药性。因此,辅助镇痛药在癌症相关疼痛的治疗中可发挥重要作用。例如,卡马西平(CBZ)可能有效,但前提是患者能够口服药物,因为它仅限于口服给药。在本研究中,我们调查了医院制剂中含CBZ片剂的栓剂的疗效。我们选择了聚乙二醇(P)、Witepsol VOSCO(®) H - 15(H)或Witepsol VOSCO(®) S - 55(S)作为栓剂基质。根据给药途径和治疗方法随机分为六至八个体外和体内组:静脉注射(i.v.)、口服(p.o.)和直肠给药(i.r.)(由CBZ粉末和片剂制剂组成,即CBZp和CBZt),分别以P、H或S为基质制备(CBZp/P、CBZp/H、CBZp/S、CBZt/P、CBZt/H和CBZt/S)。CBZt栓剂组的硬度水平显著低于CBZp栓剂组。CBZt栓剂组的药物释放曲线按P、H和S的顺序较高;这些组与CBZp栓剂组之间无显著差异。与口服组相比,CBZt栓剂组的最大药物浓度时间水平显著增加。这两组的最大药物浓度和生物利用度水平相当。这些结果表明,含CBZ片剂的栓剂可用于医院制剂。