Concomitant use of magnesium oxide significantly decreases absorption of levodopa preparations in patients with Parkinson’s disease
Introduction: Constipation is one of the most frequent non-motor symptoms of Parkinson's disease (PD), and magnesium oxide (MgO) is a frequently used laxative. This study aimed to investigate the effect of concomitant use of MgO on the pharmacokinetics of levodopa preparations in patients with...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Clinical Parkinsonism & Related Disorders |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590112523000452 |
| _version_ | 1797401707825594368 |
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| author | Noriyuki Miyaue Hayato Yabe Masahiro Nagai |
| author_facet | Noriyuki Miyaue Hayato Yabe Masahiro Nagai |
| author_sort | Noriyuki Miyaue |
| collection | DOAJ |
| description | Introduction: Constipation is one of the most frequent non-motor symptoms of Parkinson's disease (PD), and magnesium oxide (MgO) is a frequently used laxative. This study aimed to investigate the effect of concomitant use of MgO on the pharmacokinetics of levodopa preparations in patients with PD. Methods: We prospectively enrolled 35 patients with PD and compared the pharmacokinetics of levodopa and carbidopa and motor symptoms with and without MgO. The impact of alterations in pH and the addition of MgO on the solubility of levodopa formulations were also evaluated under in vitro conditions. Results: Concomitant use of MgO significantly reduced the maximum plasma concentration of levodopa (Cmax) (from 7.66 ± 3.74 μmol/L to 5.82 ± 3.69 μmol/L; p = 0.006) and area under the plasma concentration–time curve 3 h after drug administration (AUC3h, from 9.64 ± 3.23 μmol·h/L to 7.39 ± 3.15 μmol·h/L; p < 0.001), and further decreased carbidopa Cmax (from 64.02 ± 27.02 ng/mL to 38.83 ± 21.94 μmol/L; p < 0.001) and AUC3h (from 130.58 ± 65.64 ng/mL to 76.48 ± 52.24 ng·h/mL; p < 0.001). The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III score also deteriorated significantly (from 30.71 ± 11.34 to 32.06 ± 11.22; p = 0.007). MgO significantly affected the pharmacokinetics of levodopa and carbidopa. This also applied when the findings were analyzed by sex and age. In vitro dissolution experiments revealed a decrease in the relative concentrations of levodopa, carbidopa, and benserazide as the pH increased and in the presence of MgO suspension, with the most prominent impact on benserazide. Conclusions: Concomitant use of MgO and levodopa should be discouraged to improve levodopa absorption. |
| first_indexed | 2024-03-09T02:13:59Z |
| format | Article |
| id | doaj.art-a8e48baccc5a4afe8770c1366c660ae8 |
| institution | Directory Open Access Journal |
| issn | 2590-1125 |
| language | English |
| last_indexed | 2024-03-09T02:13:59Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Clinical Parkinsonism & Related Disorders |
| spelling | doaj.art-a8e48baccc5a4afe8770c1366c660ae82023-12-07T05:30:14ZengElsevierClinical Parkinsonism & Related Disorders2590-11252023-01-019100227Concomitant use of magnesium oxide significantly decreases absorption of levodopa preparations in patients with Parkinson’s diseaseNoriyuki Miyaue0Hayato Yabe1Masahiro Nagai2Department of Clinical Pharmacology and Therapeutics, Ehime University Graduate School of Medicine, Tohon, Ehime, Japan; Department of Neurology, Saiseikai Matsuyama Hospital, Matsuyama, Ehime, Japan; Corresponding author at: Department of Clinical Pharmacology and Therapeutics, Ehime University Graduate School of Medicine, Tohon, Ehime 791-0295, Japan.Department of Neurology, Saiseikai Matsuyama Hospital, Matsuyama, Ehime, JapanDepartment of Clinical Pharmacology and Therapeutics, Ehime University Graduate School of Medicine, Tohon, Ehime, JapanIntroduction: Constipation is one of the most frequent non-motor symptoms of Parkinson's disease (PD), and magnesium oxide (MgO) is a frequently used laxative. This study aimed to investigate the effect of concomitant use of MgO on the pharmacokinetics of levodopa preparations in patients with PD. Methods: We prospectively enrolled 35 patients with PD and compared the pharmacokinetics of levodopa and carbidopa and motor symptoms with and without MgO. The impact of alterations in pH and the addition of MgO on the solubility of levodopa formulations were also evaluated under in vitro conditions. Results: Concomitant use of MgO significantly reduced the maximum plasma concentration of levodopa (Cmax) (from 7.66 ± 3.74 μmol/L to 5.82 ± 3.69 μmol/L; p = 0.006) and area under the plasma concentration–time curve 3 h after drug administration (AUC3h, from 9.64 ± 3.23 μmol·h/L to 7.39 ± 3.15 μmol·h/L; p < 0.001), and further decreased carbidopa Cmax (from 64.02 ± 27.02 ng/mL to 38.83 ± 21.94 μmol/L; p < 0.001) and AUC3h (from 130.58 ± 65.64 ng/mL to 76.48 ± 52.24 ng·h/mL; p < 0.001). The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III score also deteriorated significantly (from 30.71 ± 11.34 to 32.06 ± 11.22; p = 0.007). MgO significantly affected the pharmacokinetics of levodopa and carbidopa. This also applied when the findings were analyzed by sex and age. In vitro dissolution experiments revealed a decrease in the relative concentrations of levodopa, carbidopa, and benserazide as the pH increased and in the presence of MgO suspension, with the most prominent impact on benserazide. Conclusions: Concomitant use of MgO and levodopa should be discouraged to improve levodopa absorption.http://www.sciencedirect.com/science/article/pii/S2590112523000452Parkinson's diseaseLevodopaMagnesium oxidePharmacokineticsCarbidopa |
| spellingShingle | Noriyuki Miyaue Hayato Yabe Masahiro Nagai Concomitant use of magnesium oxide significantly decreases absorption of levodopa preparations in patients with Parkinson’s disease Clinical Parkinsonism & Related Disorders Parkinson's disease Levodopa Magnesium oxide Pharmacokinetics Carbidopa |
| title | Concomitant use of magnesium oxide significantly decreases absorption of levodopa preparations in patients with Parkinson’s disease |
| title_full | Concomitant use of magnesium oxide significantly decreases absorption of levodopa preparations in patients with Parkinson’s disease |
| title_fullStr | Concomitant use of magnesium oxide significantly decreases absorption of levodopa preparations in patients with Parkinson’s disease |
| title_full_unstemmed | Concomitant use of magnesium oxide significantly decreases absorption of levodopa preparations in patients with Parkinson’s disease |
| title_short | Concomitant use of magnesium oxide significantly decreases absorption of levodopa preparations in patients with Parkinson’s disease |
| title_sort | concomitant use of magnesium oxide significantly decreases absorption of levodopa preparations in patients with parkinson s disease |
| topic | Parkinson's disease Levodopa Magnesium oxide Pharmacokinetics Carbidopa |
| url | http://www.sciencedirect.com/science/article/pii/S2590112523000452 |
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