Impact of the catechol -O -methyltransferase Val158Met polymorphism on the pharmacokinetics of l -dopa and its metabolit
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NEUROLOGY AND PRECLINICAL NEUROLOGICAL STUDIES - ORIGINAL ARTICLE
Impact of the catechol‑O‑methyltransferase Val158Met polymorphism on the pharmacokinetics of l‑dopa and its metabolite 3‑O‑methyldopa in combination with entacapone Joe Yamamoto1 · Tomohiro Omura2,6 · Sachiko Kasamo3 · Shota Yamamoto2 · Masayoshi Kawata2 · Atsushi Yonezawa2 · Yosuke Taruno4 · Hisako Endo5 · Hitoshi Aizawa5,7 · Nobukatsu Sawamoto4 · Kazuo Matsubara2,8 · Ryosuke Takahashi4 · Yoshikazu Tasaki1 Received: 4 September 2020 / Accepted: 9 October 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract In the pharmacotherapy of patients with Parkinson’s disease (PD), entacapone reduces the peripheral metabolism of l-dopa to 3-O-methyldopa (3-OMD), thereby prolonging the half-life (t1/2) of l-dopa and increasing the area under the concentration curve (AUC). The effect of entacapone on the pharmacokinetics of l-dopa differs between patients with high-activity (H/H) and low-activity (L/L) catechol-O-methyltransferase (COMT) Val158Met polymorphisms, but the effects are unclear in heterozygous (H/L) patients. 3-OMD has a detrimental effect and results in a poor response to l-dopa treatment in patients with PD; however, the influence of this polymorphism on the production of 3-OMD remains unknown. Therefore, the present study aimed to clarify the effect of the COMT Val158Met polymorphism on the concentrations of l-dopa and 3-OMD in the presence of entacapone. We performed an open-label, single-period, single-sequence crossover study at two sites in Japan. The study included 54 Japanese patients with PD, who underwent an acute l-dopa administration test with and without 100 mg entacapone on two different days. Entacapone increased l-dopa AUC0–infinity by 1.59 ± 0.26-fold in the H/H group, which was significantly higher than that in the H/L (1.41 ± 0.36-fold) and L/L (1.28 ± 0.21-fold) groups (p
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