Evans P R, Bak Y T, Kellow J E
Department of Medicine, Royal North Shore Hospital, Sydney, Australia.
Aliment Pharmacol Ther. 1996 Oct;10(5):787-93. doi: 10.1046/j.1365-2036.1996.61203000.x.
Despite its widespread use in irritable bowel syndrome (IBS), limited clinical data exist on the effects of mebeverine hydrochloride on gastrointestinal motility. Human motor activity in the small bowel is more reproducible than that in the large bowel; therefore the aim of this study was to determine in the small bowel the effects of oral mebeverine in both IBS patients and in healthy controls.
Twelve IBS patients (11 females/1 male, 46 +/- 13 years old)-predominant constipation (IBS-C, n = 6) and predominant diarrhoea (IBS-D, n = 6)-and six healthy controls, underwent continuous 48 h ambulant recording of small bowel motor activity. One low energy (400 kcal) and one high energy (800 kcal) standard meal were administered in each consecutive 24-h period. Subjects received, in blinded fashion, placebo tablets in the first 24 h then mebeverine 135 mg q.d.s. in the second 24 h.
Mebeverine had no effect on parameters of small bowel motility in controls. In contrast, in both IBS-C (P = 0.01) and IBS-D (P < 0.05) patients, phase 2 motility index was increased during mebeverine administration. Also, after mebeverine the proportion of the migrating motor complex cycle occupied by phase 2 was reduced in IBS-D (P = 0.01), while phase 2 burst frequency was reduced in IBS-C (P < 0.05). For phase 3 motor activity in IBS-C patients, the propagation velocity was decreased (P < 0.01), and the duration increased (P < 0.01).
These findings suggest that mebeverine, in the initial dosing period, has a normalizing effect in the small bowel in IBS, enhancing contractile activity in a similar fashion to 'prokinetic' agents, as well as producing alterations in motor activity consistent with an 'antispasmodic' effect.
尽管盐酸美贝维林在肠易激综合征(IBS)中广泛应用,但关于其对胃肠动力影响的临床数据有限。小肠的人体运动活性比大肠更具可重复性;因此,本研究的目的是确定口服美贝维林对IBS患者和健康对照者小肠的影响。
12例IBS患者(11例女性/1例男性,46±13岁)——以便秘为主型(IBS-C,n = 6)和以腹泻为主型(IBS-D,n = 6)——以及6名健康对照者,接受了为期48小时的小肠运动活性连续动态记录。在每个连续的24小时时间段内给予一顿低能量(400千卡)和一顿高能量(800千卡)标准餐。受试者在盲法状态下,第1个24小时服用安慰剂片,然后在第2个24小时服用135毫克美贝维林,每日4次。
美贝维林对对照组小肠动力参数无影响。相比之下,在IBS-C患者(P = 0.01)和IBS-D患者(P < 0.05)中,服用美贝维林期间2期动力指数均升高。此外,美贝维林治疗后,IBS-D患者中2期占移行性运动复合波周期的比例降低(P = 0.01),而IBS-C患者中2期爆发频率降低(P < 0.05)。对于IBS-C患者的3期运动活性,传播速度降低(P < 0.01),持续时间增加(P < 0.01)。
这些发现表明,在初始给药期,美贝维林对IBS患者的小肠具有正常化作用,以与“促动力”药物相似方式增强收缩活性,同时产生与“解痉”作用一致的运动活性改变。