ABSTRACT
BACKGROUND/AIMS: Antispasmodics such as octylonium are widely used to manage irritable bowel syndrome (IBS) symptoms. However, the efficacy and safety of another antispasmodic, tiropramide, remain uncertain. We aimed to evaluate the efficacy and safety of tiropramide compared with octylonium in patients with IBS. METHODS: In this multicenter, randomized, non-inferiority trial, 287 patients with IBS (143 receiving tiropramide and 144 octylonium) were randomly allocated to either tiropramide 100 mg or octylonium 20 mg t.i.d (means 3 times a day) for 4 weeks. Primary endpoint was the mean change of abdominal pain from baseline assessed by visual analogue scales (VAS) score after 4 weeks of treatment. Secondary endpoints were the changes in abdominal pain from baseline at week 2 and in abdominal discomfort at weeks 2 and 4, using VAS scores, patient-reported symptom improvement including stool frequency and consistency, using symptom diaries, IBS-quality of life (IBS-QoL), and depression and anxiety, at week 4. RESULTS: The VAS scores of abdominal pain at week 4, were significantly decreased in both tiropramide and octylonium groups, but the change from baseline did not differ between the 2 groups (difference,-0.26 mm; 95% CI,-4.33-3.82; P = 0.901). Abdominal pain and discomfort assessed using VAS scores, diaries, and IBS-QoL were also improved by both treatments, and the changes from baseline did not differ. The incidence of adverse events was similar in the 2 groups, and no severe adverse events involving either drug were observed. CONCLUSIONS: Tiropramide is as effective as octylonium in managing abdominal pain in IBS, with a similar safety profile.
Subject(s)
Humans , Abdominal Pain , Anxiety , Depression , Incidence , Irritable Bowel Syndrome , Parasympatholytics , Weights and MeasuresABSTRACT
AIMS OF STUDY: Present study designed to observe inhibitory effects of propiverine HC1 and tiropramide against the smooth muscle contraction of female rat bladder. Propiverine has both direct smooth muscle relaxation and anticholinergic effect and has relatively fewer side effect than conventionally used drugs such as oxybutinin. Tiropramide has been known as modulatory agents of gastrointestinal motility but also has inhibitory effects against the bladder contraction. METHODS: 30 adult female Sprague-Dawley rats were used. Bladder body above ureteral orifice was resected under pentobarbital anesthesia. 1 x 0.5 cm sized smooth muscle strip was made, and incubated in Tyrode`s solution aerated with 95% oxygen. After reaching equilibrium state, each strip was stimulated by field stimulation (FS, 1-32 Hz) and bethanechol administration (0.0000001-0.0001M). From each strip, degree of muscle contraction was recorded by physiograph (Gilson IC-MP). After the control stimulations, each strip was treated by atropine, tiropramide, oxybutinin and propiverine HC1. After 30 minutes, same stimulation were repeated and degree of muscle contraction was compared to pre incubation data. RESULTS: Frequency and dose dependent muscle contractions were noted for both FS and bethanechol stimulation. Greater degree of contractions were noted for FS than for bethanechol stimulation. Inhibitory effects of tiropramide, propiverine HC1 and oxybutinin were greater than those of atropine at FS (1-32 Hz). At high concentration (0.0001M), all of the drugs but atropine inhibited field stimulated smooth muscle contraction more than 90%. At lower concentration (0. 0000001-0.000001M), inhibitory actions of oxybutinin and propiverine HC1 were greater than that of tiropramide (p>0.05). Propiverine HC1 and oxybutinin had similar inhibitory effect for all con-centration. At higher concentration (0.0001M), inhibitory effects of tiro-pramide were more than 98% whereas those of oxybutinin and propiverine HC1 were 88%. At low concentration (0.0000001-0.000001M), oxybutinin exhibited greater inhibition against the bethanechol induced contraction than did tiropramide and propiverine HC1. With these results, it was suggested that in low concentration, oxybutinin and propiverine HCI had greater inhibitory effect than did tiropramide against smooth muscle contraction of the bladder. In high concentration though, tiropramide had superior inhibitory effect than did oxybutinin and propiverine HC1. Since, no difference was noted between oxybutinin and propiverine HC1 for the inhibitory action of bladder contraction, propiverine HC1 seems reasonable substitute for the treatment of detrusor hyperreflexia with less side effects. Also these results indicate that tiropramide can be used for the management of unstable bladder.