In patients with Parkinson disease (PD), levodopa/carbidopa therapy with a decarboxylase inhibitor (DCI) to levodopa ratio of 1:10 may delay the occurrence of subsequent motor fluctuations throughout the course of the illness, compared with levodopa/benserazide therapy with a DCI to levodopa ratio of 1:4. These are the findings of a retrospective cohort study published in the Journal of the Neurological Sciences.

The difference in the blending ratio of levodopa/DCI may impact disease progression in individuals with PD. This prompted the researchers to evaluate the duration from initiation of levodopa/DCI to the emergence of motor fluctuations in Japanese patients with PD initially treated with levodopa/benserazide 300/75 mg/day or levodopa/carbidopa 300/30 mg/day.

Only 2 formulations of immediate-release levodopa with distinct ratios of DCI are available in Japan for the treatment of PD — levodopa/benserazide 100/25 mg and levodopa/carbidopa 100/10 mg. The relationship between the difference in DCI to levodopa ratio and the development of PD-associated motor complications with long-term levodopa therapy remains to be fully elucidated.


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Among a total of 186 candidate patients with PD, 52 fulfilled the selection criteria and were enrolled in the current study. Of the 52 participants, 20 initially received levodopa/benserazide 300/75 mg/day and 32 received levodopa/carbidopa 300/30 mg/day.

No significant difference was reported in the mean duration from onset of motor symptoms to diagnosis of PD and initiation of levodopa treatment between the levodopa/benserazide group and the levodopa/carbidopa group (1.6±1.1 years vs 1.6±1.0 years, respectively). The mean duration from initiation of levodopa/DCI therapy to emergence of motor fluctuations, however, was significantly longer in the levodopa/ carbidopa arm than in the levodopa/benserazide arm (5.0±1.4 years vs 3.1±1.2 years, respectively; P <.01). Further, the mean duration from onset of motor symptoms to emergence of motor fluctuations in the levodopa/carbidopa group was also significantly longer than in the levodopa/benserazide group (6.6±1.6 years vs 4.7±1.3 years, respectively; P <.01).

The subtypes of motor fluctuations in the levodopa/benserazide arm included wearing off in 85.0% (17 of 20) of participants and on-off fluctuations in 15.0% (3 of 20) of patients. In contrast, in the levodopa/carbidopa group, the subtypes of motor fluctuations included wearing off in 84.4% (27 of 32) of participants, on-off fluctuations in 12.5% (4 of 32) of patients, and a sudden off period in 3.1% (1 of 32) of participants.

A limitation of the current study is that it involved a survey, which may have introduced the possibility that the treatment bias of each physician impacted the evaluation of progression of individual motor symptoms. This could have potentially led to the difference in the time to the emergence of motor fluctuations cannot be discounted.

“Further large-scale studies are needed to elucidate the relationship between the blending ratio of levodopa/DCI and disease progression in PD,” the researchers concluded.

Disclosure: None of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies.  

Reference

Baba Y, Futamura A, Kinno R, et al. The relationship between the distinct ratios of benserazide and carbidopa to levodopa and motor complications in Parkinson’s disease: a retrospective cohort study. J Neurol Sci. Published online April 18, 2022. doi:10.1016/j.jns.2022.120263