A Phase I Study Evaluating Tolerability, Pharmacokinetics, and Preliminary Efficacy of L‐Menthol in Upper Gastrointestinal Endoscopy

  title={A Phase I Study Evaluating Tolerability, Pharmacokinetics, and Preliminary Efficacy of L‐Menthol in Upper Gastrointestinal Endoscopy},
  author={Naoki Hiki and Michio Kaminishi and Tomoko Hasunuma and M. Nakamura and Sachiyo Nomura and Naohisa Yahagi and Hisao Tajiri and H. Suzuki},
  journal={Clinical Pharmacology \& Therapeutics},
Peppermint oil has been shown to relax gastrointestinal smooth muscle. In this randomized, placebo‐controlled study, an L‐menthol preparation, NPO‐11, was assessed for tolerability and pharmacokinetics (PK) during gastrointestinal endoscopy. Single doses of NPO‐11, as high as 320 mg, were well tolerated. NPO‐11 was rapidly absorbed, with peak concentrations reached within 1 h after administration. Approximately 70% of the administered L‐menthol and its metabolites were excreted in the urine… 

The absorption and metabolism of a single L-menthol oral versus skin administration: Effects on thermogenesis and metabolic rate.

  • A. ValenteA. E. Carrillo A. Flouris
  • Medicine, Biology
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2015

Efficacy of spraying l-menthol solution during endoscopic treatment of early gastric cancer: a phase III, multicenter, randomized, double-blind, placebo-controlled study

During gastric endoscopic submucosal dissection, spraying l-menthol on the gastric mucosa significantly suppressed peristalsis, with minimal adverse drug reactions as compared with placebo.

A Novel Ileocolonic Release Peppermint Oil Capsule for Treatment of Irritable Bowel Syndrome: A Phase I Study in Healthy Volunteers

IC-PO has a significantly delayed peak menthol glucuronide concentration and Tlag, both pointing to the release of PO in the more distal part of the intestine, which may enhance therapeutic efficacy.

Antiperistaltic effect and safety of l‐menthol oral solution on gastric mucosa for upper gastrointestinal endoscopy in Chinese patients: Phase III, multicenter, randomized, double‐blind, placebo‐controlled study

The efficacy and safety of a single dose l‐menthol solution in suppressing gastric peristalsis during upper GI endoscopy in Chinese patients is evaluated.

Preclinical disposition of MGS0274 besylate, a prodrug of a potent group II metabotropic glutamate receptor agonist MGS0008 for the treatment of schizophrenia

Results suggested that MGS0274 was, as expected, presystemically hydrolyzed to MGS0008 after gastrointestinal absorption and that M GS0008 was distributed throughout the body without further metabolism and ultimately excreted in urine in the animals.

An In-Silico Investigation of Menthol Metabolism

This in silico approach is based on the three in vivo studies and aims to resolve the discrepancies in proposed pathways of (-)-menthol metabolism and fills missing links in previously published pathways.

An in silico investigation of menthol metabolism

This in silico approach is based on the three in vivo studies and aims to resolve the discrepancies in proposed pathways of (-)-menthol metabolism and fills missing links in previously published pathways.

L-Menthol for Gastrointestinal Endoscopy: A Systematic Review and Meta-Analysis

The findings of this study support the use of L-menthol to suppress gastrointestinal peristalsis during endoscopic procedure.

Evaluation of mint efficacy regarding dysmenorrhea in comparison with mefenamic acid: A double blinded randomized crossover study

Pain and its severity and all the clinical signs and symptoms decreased after taking peppermint extract, and using mint is advised for treating dysmenorrhea symptoms.

The safety evaluation of food flavouring substances: the role of metabolic studies.

The types of metabolic reactions that have been documented for flavour substances that are added to the human food chain, the methodologies available for metabolic studies, and the factors that affect the metabolic fate of a flavour substance are summarized.



Gastrointestinal clinical pharmacology of peppermint oil.

Metabolic fate of [3H]-l-menthol in the rat.

The results have enabled the construction of a metabolic map for menthol in the rat that provides the basis for structure-metabolism relationships describing the fate of numerous menthol congeners of flavor importance.

Studies on the metabolism of l-menthol in rats.

Repeated oral administration of l-menthol to rats for 3 days resulted in the increase of both liver microsomal cytochrome P-450 content and NADPH-cytochrome c reductase activity by nearly 80%.

Dermal Absorption of Camphor, Menthol, and Methyl Salicylate in Humans

Although unable to determine the absolute dermal bioavailability of these compounds, there appears to be relatively low systemic exposure to these potentially toxic compounds, even when an unrealistically large number of patches are applied for an unusually long time.

Pharmacokinetics of menthol and carvone after administration of an enteric coated formulation containing peppermint oil and caraway oil.

The pharmacokinetics of menthol and carvone after oral administration of the two formulations were studied in a randomized, two-period cross-over study in 16 healthy male volunteers to confirm bioequivalence.

Peppermint oil enhances cyclosporine oral bioavailability in rats: comparison with D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS) and ketoconazole.

The lack of a significant ketoconazole effect may reflect poor metabolism of cyclosporine in rat intestinal tissue and suggests that inhibition of cytochrome P450 3A is not the only means by which peppermint oil enhances cyclosporaine oral bioavailability.

Peppermint oil reduces gastric spasm during upper endoscopy: a randomized, double-blind, double-dummy controlled trial.

Peppermint oil solution administered intraluminally can be used as an antispasmodic agent with superior efficacy and fewer side effects than hyoscine-N-butylbromide administered by intramuscular injection during upper endoscopy.

The actions of peppermint oil and menthol on calcium channel dependent processes in intestinal, neuronal and cardiac preparations

The data indicate that both menthol and peppermint oil exert Ca2+ channel blocking properties which may underlie their use in irritable bowel syndrome.

Disposition kinetics and effects of menthol

A crossover placebo‐controlled study was conducted that compared pure menthol versus placebo, along with an uncontrolled exposure to menthol in food or beverage, to determine the disposition kinetics and to examine subjective and cardiovascular effects of menthol.

Delayed hypersensitivity reaction after intravenous glucagon administered for a barium enema: a case report.

A patient with delayed hypersensitivity reaction after barium enema is reported and the potential of glucagon to cause hypersensitivity reactions is highlighted.