Product Information
Registration Status: ActiveCEREKINON TABLET 100mg is approved to be sold in Singapore with effective from 1989-04-17. It is marketed by MITSUBISHI TANABE PHARMA SINGAPORE PTE LTD, with the registration number of SIN02518P.
This product contains Trimebutine 100mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by Mitsubishi Tanabe Pharma Factory Ltd in JAPAN.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Trimebutine is a spasmolytic agent that regulates intestinal and colonic motility and relieves abdominal pain with antimuscarinic and weak mu opioid agonist effects. It is marketed for the treatment of irritable bowel syndrome (IBS) and lower gastrointestinal tract motility disorders, with IBS being one of the most common multifactorial GI disorders [A19691]. It is used to restore normal bowel function and is commonly present in pharmaceutical mixtures as trimebutine maleate salt form. Trimebutine is not a FDA-approved drug, but it is available in Canada and several other international countries.
Indication
Indicated for symptomatic treatment of irritable bowel syndrome (IBS) and treatment of postoperative paralytic ileus following abdominal surgery.
Mechanism of Action
At high concentrations, trimebutine is shown to inhibit the extracellular Ca2+ influx in the smooth muscle cells through voltage dependent L-type Ca2+ channels and further Ca2+ release from intracellular Ca2+ stores [A19691, A19689]. Trimebutine is suggested to bind to the inactivated state of the calcium channel with high affinity. Reduced calcium influx attenuates membrane depolarization and decrease colon peristalsis. It also inhibits outward K+ currents in response to membrane depolarization of the GI smooth muscle cells at resting conditions through inhibition of delayed rectifier K+ channels and Ca2+ dependent K+ channels, which results in induced muscle contractions [A19691, A19695]. Trimebutine binds to mu opioid receptors with more selectivity compared to delta or kappa opioid receptors but with lower affinity than their natural ligands. Its metabolites (N-monodesmethyl-trimebutine or nor-trimebutine), are also shown to bind to opoid receptors on brain membranes and myenteric synaptosomes [A19692].
Pharmacokinetics
- Absorption
- The free base form or salt form of trimebutine are rapidly absorbed after oral administration, with the peak plasma concentration reached after 1 hour of ingestion [A19692]. The time to reach peak plasma concentration following a single oral dose of 200mg trimebutine is 0.80 hours [L872].
- Distribution
- Trimebutine is most likely to be accumulated in the stomach and the intestinal walls in highest concentrations. The fetal transfer is reported to be low [A19692].
- Metabolism
- Trimebutine undergoes extensive hepatic first-pass metabolism. Nortrimebutine, or N-monodesmethyltrimebutine, is the main metabolite that retains pharmacological activity on the colon. This metabolite can undergo second N-demethylation to form N-didesmethyltrimebutine. Other main urinary metabolites (2-amino, 2-methylamino or 2-dimethylamino-2-phenylbutan-1-ol) can be formed via hydrolysis of the ester bond of desmethylated metabolites or initial hydrolysis of the ester bond of trimebutine followed by sequential N-demethylation [A19694]. Trimebutine is also prone to sulphate and/or glucuronic acid conjugation [L872].
- Elimination
Toxicity
Common gastrointestinal adverse effects include dry mouth, foul taste, diarrhea, dyspepsia, epigastric pain, nausea and constipation. Some CNS effects include drowsiness, fatigue, dizziness, hot/cold sensations and headaches. In case of overdosage, gastric lavage is recommended. Oral LD50 in mouse and rats is >5000 mg/kg and 2500 mg/kg in rabbits, respectively. Trimebutine is not reported to display teratogenic, mutagenic or carcinogenic potential [L872].
Active Ingredient/Synonyms
2-Dimethylamino-2-phenylbutyl 3,4,5-trimethoxybenzoat | Trimébutine | Trimebutino | Trimebutine |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.