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

Abstract

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, and this amount fluctuated with no change in the dose. The principal metabolite identified in plasma and urine was menthol glucuronide. The other metabolites include mono- or di-hydroxylated menthol derivatives, most of which are excreted, in part, as glucuronic acid conjugates. The pharmacokinetic data indicated that when NPO-11 is sprayed directly onto the gastric mucosa, it is rapidly metabolized to glucuronic acid conjugates that are excreted in urine. The findings from this study provide new data on the safety and PK of NPO-11 and support further trials.

Encapsulation of l-menthol in hydroxypropyl-β-cyclodextrin and release characteristics of the inclusion complex

“…x l-menthol-HP-β-CD (s) → y l-menthol (g) + + z HP-β-CD (s) (2) The rate expression for the disappearance of l-menthol--HP-β-CD in the reaction as shown in Eq. (2) may be expressed by: (3) where α is the fraction of l-menthol-HP-β-CD decomposed at time t, n is the order of reaction, and k is the rate constant.…”

“…In certain medications, l-menthol is used to treat sunburns, as it provides a cooling sensation. l-menthol is also included in nonprescription products for short-term relief of minor sore throat and minor mouth or throat irritation 3 . Furthermore, l-menthol can reduce incidence rates of a variety of cancers (e.g.…”

Menthol Smokers: Metabolomic Profiling and Smoking Behavior

“…Benowitz et al has reported urine levels of the MG as biomarker of exposure in menthol smokers with an improved method by liquid chromatography–mass spectrometry (54). Other study have reported the assessment of MG in humans related menthol in the treatment of gastrointestinal disease using gas chromatography–mass spectrometry in urine and plasma (53, 55, 56). In this study, by using a robust method UPLC-Q-TOF MS which allows better separation and resolution for the untargeted metabolomics, MG was detected simultaneously with smokers’ metabolomics profiles.…”

Menthol differs from other terpenic essential oil constituents

“…Human plasma levels of intact menthol after oral administration were either not detectable or only in quantities less than 1% of the major metabolite, menthol glucuronide (Gelal et al, 1999;Hiki et al, 2011), suggesting a very efficient first-pass glucuronidation of menthol at the free hydroxyl group by e.g. UDP-glucuronosyltransferase 2B7 (Coffman et al, 1998).…”