Mebeverine, a gastrointestinal antispasmodic drug used to treat irritable bowel syndrome (IBS) and functional bowel disorders, was developed in the 1960s and introduced into clinical use in the following decades. Its history is marked by its effectiveness in relieving abdominal pain, cramping, and bowel spasms without significantly affecting normal gut motility. Mebeverine, a direct smooth muscle relaxant, acts primarily on the intestinal smooth muscle to reduce hypercontractility and discomfort associated with IBS. It is widely used as a symptomatic treatment option and is included in various international guidelines for managing functional gastrointestinal disorders. Unlike many systemic antispasmodics, mebeverine has a favorable safety profile with minimal anticholinergic side effects, contributing to its long-standing clinical use.
BRAND NAMES
Duspatalin
Colofac
Colotal
MECHANISM OF ACTION
Mebeverine is a direct-acting antispasmodic that acts on the smooth muscles of the gastrointestinal tract. It works by inhibiting calcium ion influx into smooth muscle cells and reducing intracellular calcium availability, which leads to relaxation of intestinal smooth muscle. Unlike anticholinergic drugs, mebeverine does not significantly affect muscarinic receptors, so it does not produce typical anticholinergic side effects such as dry mouth or blurred vision.
PHARMACOKINETICS
Absorption
However, it undergoes extensive first-pass metabolism in the liver and intestinal wall, resulting in very low systemic bioavailability of the unchanged drug. Peak plasma concentrations are usually reached within 1 to 3 hours.
Distribution
The apparent volume of distribution is estimated to be moderate to large, approximately in the range of 1–3 L/kg (varies among sources and studies). This reflects extensive tissue distribution, despite low systemic availability of unchanged mebeverine.
Metabolism
Mebeverine undergoes rapid and almost complete metabolism in the liver and intestinal wall after oral administration, primarily through ester hydrolysis. The main metabolic pathway converts mebeverine into its active metabolite, veratric acid, and other inactive alcohol derivatives. These metabolites may undergo further phase II conjugation reactions such as glucuronidation.
Elimination
Mebeverine is eliminated mainly after extensive metabolism, with the majority of its metabolites excreted through the kidneys in urine. A smaller proportion is excreted via the bile into feces.
PHARMACODYNAMICS
Mebeverine acts directly on the smooth muscle of the gastrointestinal tract to relieve spasms without affecting normal gut motility. It works by inhibiting calcium influx into smooth muscle cells and reducing intracellular calcium availability, which decreases muscle contraction. It may also stabilize sodium channels in intestinal smooth muscle, reducing hyperexcitability and abnormal contractions.
ADMINISTRATION
Mebeverine is administered orally in the form of tablets or modified-release capsules. It is usually taken before meals to achieve better control of gastrointestinal spasms. The tablets or capsules should be swallowed whole with water and should not be chewed or crushed, especially in modified-release formulations.
DOSAGE AND STRENGTH
Mebeverine is available mainly in 135 mg immediate-release tablets and 200 mg modified-release (MR) capsules. The usual adult dosage for immediate-release tablets is 135 mg taken three times daily, preferably before meals. For modified-release capsules, the typical dose is 200 mg taken twice daily, usually in the morning and evening.
DRUG INTERACTIONS
Mebeverine has relatively few clinically significant drug interactions due to its extensive first-pass metabolism and minimal systemic exposure. However, theoretical interactions may occur with drugs that affect hepatic metabolism, although no major cytochrome P450–mediated interactions are well established.
FOOD INTERACTIONS
Mebeverine has no clinically significant food interactions. However, it is commonly recommended to take the medication before meals, as this timing helps provide better control of postprandial gastrointestinal spasms and symptoms of irritable bowel syndrome.
CONTRAINDICATIONS
Mebeverine is contraindicated in patients with known hypersensitivity to mebeverine hydrochloride or any of its excipients. It should be used with caution in individuals with a history of allergic reactions to similar antispasmodic agents. The drug is generally not recommended in children unless prescribed by a physician due to limited safety data.
SIDE EFFECTS
Nausea
Dizziness
Headache
Indigestion (dyspepsia)
Constipation (less common)
Diarrhea (less common)
Mild abdominal discomfort.
OVER DOSE
Mebeverine overdose is rare, but excessive intake may lead to mild to moderate gastrointestinal and neurological symptoms. Reported effects include nausea, vomiting, abdominal pain, and dizziness. In some cases, mild central nervous system stimulation or depression may occur.
TOXICITY
Mebeverine toxicity is uncommon because the drug undergoes rapid and extensive first-pass metabolism, resulting in low systemic exposure. Even in overdose situations, serious toxic effects are rare. Reported toxicity mainly involves gastrointestinal symptoms such as nausea, vomiting, and abdominal pain, along with occasional dizziness or mild central nervous system effects.
