title: 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.
authors.affiliation: Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. naoki.hiki@jfcr.or.jp
authors.forename: N
authors.initials: N
authors.lastname: Hiki
authors.forename: M
authors.initials: M
authors.lastname: Kaminishi
authors.forename: T
authors.initials: T
authors.lastname: Hasunuma
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Nomura
authors.forename: N
authors.initials: N
authors.lastname: Yahagi
authors.forename: H
authors.initials: H
authors.lastname: Tajiri
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D016099:Endoscopy, Gastrointestinal / Q000379:methods*; D005753:Gastric Mucosa / Q000378:metabolism*; D005965:Glucuronates / Q000493:pharmacokinetics*; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008610:Menthol / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008875:Middle Aged
chemical_list: D005965:Glucuronates; D008610:Menthol; C044963:menthol glucuronide