Oral bioavailability and enterohepatic recirculation of otilonium bromide in rats

  title={Oral bioavailability and enterohepatic recirculation of otilonium bromide in rats},
  author={Beom Soo Shin and Jung Jun Kim and John Kim and S K Hu and Han Kyung Kim and Hye Suk Lee and Sun Dong Yoo},
  journal={Archives of Pharmacal Research},
This study was conducted to examine the oral bioavailability and the possibility of enterohepatic recirculation of otilonium bromide in rats. A sensitive LC/MS/MS assay (LLOQ 0.5 ng/mL) was developed for the determination of otilonium and applied to i.v. and oral administration studies in bile duct cannulated (BDC) and non-BDC rats. After i.v. injection to BDC rats (1 mg/kg as otilonium), average t1/2, CL, Vz and AUC were 7.9 ± 1.9 h, 8.7 ± 3.1 mL/min/kg, 5.7 ± 1.4 L/kg and 2,088 ± 676 ng·h/mL… 
Determination of the unstable drug otilonium bromide in human plasma by LC-ESI-MS and its application to a pharmacokinetic study.
  • Yan-Rong Zhao, L. Ding, Ya-Kun Rao
  • Biology, Chemistry
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
  • 2010
Multiple Peaking Phenomena in Pharmacokinetic Disposition
Each of the most common sources of multiple peaking is contributed by biliary secretion followed by intestinal reabsorption of a drug, a process for which the term ‘enterohepatic recycling’ has been coined.
A Mini Review on Characteristics and Analytical Methods of Otilonium Bromide.
Otilonium bromide (OTB) is quaternary ammonium compound with action on distal GI tract as antispasmodic and is utilized in the treatment of patients influenced by Irritable inside disorder (IBS because of its particular pharmacokinetic and pharmacodynamic properties.
Development and validation of a stability-indicating RP-LC method for the simultaneous determination of otilonium bromide and its expected degradation product in bulk drug and pharmaceutical preparation
A simple, precise, accurate and rapid stability indicating liquid chromatography method had been developed for the simultaneous determination of otilonium bromide (OB) and its expected degradation
Long-term efficacy and safety of otilonium bromide in the management of irritable bowel syndrome: a literature review
OB is a poorly absorbed spasmolytic drug, exerting significantly greater control of the symptoms of IBS compared with placebo, suggesting that the drug could effectively be used for the long-term management of patients with IBS.
Changes in nitrergic and tachykininergic pathways in rat proximal colon in response to chronic treatment with otilonium bromide
  • G. Cipriani, S. Gibbons, G. Farrugia
  • Medicine
    Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
  • 2015
Otilonium bromide is used as a spasmolytic drug in the treatment of the functional bowel disorder irritable bowel syndrome but little is known about the effects of chronic administration of OB on enteric neurons, neuromuscular transmission, and interstitial cells of Cajal, key regulators of the gut function.
Colonic smooth muscle cells and colonic motility patterns as a target for irritable bowel syndrome therapy: mechanisms of action of otilonium bromide
Otilonium bromide inhibits the main patterns of human sigmoid motility in vitro, which are spontaneous rhythmic phasic contractions, smooth muscle tone, contractions induced by stimulation of excitatory motor neurons and contraction induced by direct effect of excited neurotransmitters, thereby limiting excessive intestinal contractility and abdominal cramping.
Effect of otilonium bromide on contractile patterns in the human sigmoid colon
  • D. Gallego, M. Aulí, P. Clavé
  • Medicine
    Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
  • 2010
The aim of this study was to characterize the pharmacological effects of OB on contractile patterns in the human sigmoid colon.


A distribution study with (14)C-otilonium bromide in the rat: evidence for selective tropism for large intestine after oral administration.
Oral administered (14)C-otilonium bromide is poorly absorbed systemically, as indicated by the very low plasma radioactivity levels, but it is able to effectively penetrate into the large intestine walls, a recognized target for drugs oriented toward irritable bowel syndrome therapy.
The clinical phcarmacology of single doses of otilonium bromide in healthy volunteers
Otilonium bromide was well tolerated at all doses, due mainly to low systemic absorption, and seems unlikely to achieve physiological or clinical significance.
Simultaneous determination of otilonium bromide and diazepam by first-derivative spectroscopy.
A rapid, simple assay procedure was developed for simultaneous analysis of otilonium bromide, a smooth-muscle relaxant, and diazepam in tablets containing 20 and 40 mg by "zero-crossing" first-derivative spectroscopy, and the results were in good agreement.
Otilonium Bromide: A Selective Spasmolytic for the Gastrointestinal Tract
  • S. Evangelista
  • Medicine
    The Journal of international medical research
  • 1999
Clinical studies have confirmed OB as a potent spasmolytic drug with a good tolerability profile and studies in patients with irritable bowel syndrome demonstrated OB to be superior to placebo and reference drugs in parameters such as pain, abdominal distension and motility.
Pharmacological studies on otilonium bromide.
  • A. Giachetti
  • Biology, Medicine
    The Italian journal of gastroenterology
  • 1991
OB seems to exert its activity mainly on distal GI tract, and its spasmolytic effect may be due to its ability to inhibit Ca++ fluxes and to a direct action of the drug on the contractile proteins of the smooth muscle.
High-performance liquid chromatographic method for assay of otilonium bromide, diazepam, and related compounds in finished pharmaceutical forms.
A rapid, simple, stability-indicating assay procedure for otilonium bromide, a smooth muscle relaxant agent, and diazepam in composite tablet analysis was developed with high-performance liquid chromatography, demonstrating the selectivity of the chromatographic system.
Stability-indicating methods for determining omeprazole and octylonium bromide in the presence of their degradation products.
Four stability-indicating assays were developed for determining omeprazole and octylonium bromide and these methods were used to determine drugs in bulk powder, laboratory-prepared mixtures, and pharmaceutical dosage forms.
Optimisation and validation of a capillary electrophoresis method for the simultaneous determination of diazepam and otilonium bromide.
A simultaneous assay of diazepam and otilonium bromide in coated tablets by capillary zone electrophoresis (CZE) was developed and the influence of various parameters on analysis time and on the theoretical plates of the two peaks was investigated by means of experimental design.
Quaternary ammonium derivatives as spasmolytics for irritable bowel syndrome.
Taking into consideration the published trials carried out with validated methodology in irritable bowel syndrome, cimetropium and otilonium are the best demonstrated drugs for the improvement in global assessment, pain and abdominal distension.
Extended analysis of a double-blind, placebo-controlled, 15-week study with otilonium bromide in irritable bowel syndrome
The present re-evaluation of a previously published study confirms that otilonium bromide is more effective than placebo for the treatment of irritable bowel syndrome, being very efficient in relieving pain and discomfort.