Literature DB >> 35402640

Impact of Intestinal Bacteria on Levodopa Pharmacokinetics in LCIG Therapy.

Yuki Yamanishi1, Mohammed Emamussalehin Choudhury2, Akira Yoshida1, Yuko Hosokawa1, Noriyuki Miyaue1, Satoshi Tada1, Rina Ando1, Shinobu Murakami3, Hitoshi Miyamoto3, Masahiro Nagai1.   

Abstract

Background: Levodopa-carbidopa intestinal gel (LCIG) therapy is used in advanced Parkinson's disease (PD) and consists of continuous administration of levodopa directly into the jejunum through a percutaneous endoscopic gastro-jejunal (PEG-J) tube. Recently, the metabolism of levodopa by Enterococcus faecalis (E. faecalis) has been reported. Intestinal bacteria can also affect this therapy.
Objectives: To investigate intestinal bacteria and examine its impact on levodopa blood concentration in patients with PD receiving LCIG therapy.
Methods: We enrolled 6 patients receiving LCIG therapy in our department. After PEG-J tube replacement, intestinal bacteria were collected from the tip of the tube and were identified using culture and polymerase chain reaction (PCR) tests. Moreover, the presence of tyrosine decarboxylase, which metabolizes levodopa, was also confirmed by PCR test. The ability of these bacteria to metabolize levodopa was confirmed in vitro. Levodopa blood concentrations were also examined before PEG-J tube replacement.
Results: Bacteria were detected in all 6 patients. E. faecalis was present in 4 patients. Moreover, tyrosine decarboxylase was detected in 2 patients. The identified bacteria displayed in vitro metabolization to dopamine in the 4 E. faecalis positive samples. The addition of carbidopa did not inhibit the metabolism of levodopa. However, there was no difference in the mean blood concentration of levodopa, regardless of the presence of E. faecalis. Conclusions: We found bacteria, including E. faecalis in the PEG-J tube. We observed levodopa metabolism in vitro, but there was no association with levodopa blood concentration. The effect of intestinal bacteria may be limited in patients receiving LCIG therapy.
© 2022 International Parkinson and Movement Disorder Society.

Entities:  

Keywords:  LCIG; Parkinson's disease; intestinal bacteria; levodopa pharmacokinetics; neuropathology

Year:  2022        PMID: 35402640      PMCID: PMC8974876          DOI: 10.1002/mdc3.13417

Source DB:  PubMed          Journal:  Mov Disord Clin Pract        ISSN: 2330-1619


  22 in total

1.  Gastrointestinal bacterial overgrowth: pathogenesis and clinical significance.

Authors:  Amit H Sachdev; Mark Pimentel
Journal:  Ther Adv Chronic Dis       Date:  2013-09       Impact factor: 5.091

Review 2.  Small intestinal bacterial overgrowth syndrome.

Authors:  Jan Bures; Jiri Cyrany; Darina Kohoutova; Miroslav Förstl; Stanislav Rejchrt; Jaroslav Kvetina; Viktor Vorisek; Marcela Kopacova
Journal:  World J Gastroenterol       Date:  2010-06-28       Impact factor: 5.742

Review 3.  Systematic review of levodopa dose equivalency reporting in Parkinson's disease.

Authors:  Claire L Tomlinson; Rebecca Stowe; Smitaa Patel; Caroline Rick; Richard Gray; Carl E Clarke
Journal:  Mov Disord       Date:  2010-11-15       Impact factor: 10.338

4.  Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease.

Authors:  Timothy R Sampson; Justine W Debelius; Taren Thron; Stefan Janssen; Gauri G Shastri; Zehra Esra Ilhan; Collin Challis; Catherine E Schretter; Sandra Rocha; Viviana Gradinaru; Marie-Francoise Chesselet; Ali Keshavarzian; Kathleen M Shannon; Rosa Krajmalnik-Brown; Pernilla Wittung-Stafshede; Rob Knight; Sarkis K Mazmanian
Journal:  Cell       Date:  2016-12-01       Impact factor: 41.582

5.  The effect of L-leucine on the absorption of levodopa, studied by regional jejunal perfusion in man.

Authors:  H Lennernäs; D Nilsson; S M Aquilonius; O Ahrenstedt; L Knutson; L K Paalzow
Journal:  Br J Clin Pharmacol       Date:  1993-03       Impact factor: 4.335

6.  Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease.

Authors:  Sebastiaan P van Kessel; Alexandra K Frye; Ahmed O El-Gendy; Maria Castejon; Ali Keshavarzian; Gertjan van Dijk; Sahar El Aidy
Journal:  Nat Commun       Date:  2019-01-18       Impact factor: 14.919

7.  Effect of Parkinson's disease and related medications on the composition of the fecal bacterial microbiota.

Authors:  Severin Weis; Andreas Schwiertz; Marcus M Unger; Anouck Becker; Klaus Faßbender; Stefan Ratering; Matthias Kohl; Sylvia Schnell; Karl-Herbert Schäfer; Markus Egert
Journal:  NPJ Parkinsons Dis       Date:  2019-11-29

8.  The Association Between the Gut Microbiota and Parkinson's Disease, a Meta-Analysis.

Authors:  Ting Shen; Yumei Yue; Tingting He; Cong Huang; Boyi Qu; Wen Lv; Hsin-Yi Lai
Journal:  Front Aging Neurosci       Date:  2021-02-12       Impact factor: 5.750

9.  Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism.

Authors:  Vayu Maini Rekdal; Elizabeth N Bess; Jordan E Bisanz; Peter J Turnbaugh; Emily P Balskus
Journal:  Science       Date:  2019-06-14       Impact factor: 47.728

Review 10.  Minireview on the Relations between Gut Microflora and Parkinson's Disease: Further Biochemical (Oxidative Stress), Inflammatory, and Neurological Particularities.

Authors:  Ovidiu-Dumitru Ilie; Alin Ciobica; Jack McKenna; Bogdan Doroftei; Ioannis Mavroudis
Journal:  Oxid Med Cell Longev       Date:  2020-02-05       Impact factor: 6.543

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