Objective: We aimed to investigate the correlation between levodopa pharmacokinetics and levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD).

Background: In patients with PD, pulsatile dopaminergic stimulation may be a primary cause of LID. Although the levodopa pharmacokinetics has interindividual variability, no study has evaluated the relationship between the development of LID and levodopa pharmacokinetics in patients with PD.

Method: We retrospectively reviewed 255 consecutive patients with PD without LID and underwent the acute levodopa challenge test (LDCT) with 100 mg levodopa. The patients were divided into the carbidopa (10 mg) (n = 185) and benserazide (25 mg) (n = 70) groups, according to the type of peripheral decarboxylase inhibitor (DCI) used in the LDCT. The type of DCI used in the LDCT was determined by the usual prescription of the formulations of levodopa. The patients were followed-up in the outpatient clinic every 1 to 3 months after the LDCT.

Results: During a median follow-up of 32 months (IQR, 16–49 months), 73 patients (29%) developed LID. Compared with patients who did not develop LID (PD–LID−), those who developed LID (PD–LID+) were younger (p = 0.003) and had significantly higher maximum levodopa concentration (Cmax) (p = 0.002) and area under the curve (p <0.001), LEDD (p <0.001), and improvement of motor symptom in the LDCT (p = 0.009). The Cmax cutoff value that yielded the lowest possible p value for LID-free survival was 9.83 nmol/mL (log-rank, p = 0.002, Figure 1A) in the carbidopa group and 15.88 nmol/mL (log-rank, p = 0.004, Figure 1B) in the benserazide group. In the multivariate Cox proportional hazards models, these respective cutoff Cmax values were associated with incident LID in the carbidopa group (HR 2.05, 95% CI 1.09–3.84) and in the benserazide group (HR 6.42, 95% CI 2.12–19.5).

Conclusion: The present study, to our best knowledge, was the first to assess the association between the development of LID and levodopa pharmacokinetics in patients with PD. High levodopa plasma concentration in the LDCT was associated with incident LID in patients with PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/high-levodopa-plasma-concentration-in-the-acute-levodopa-challenge-test-predicts-levodopa-induced-dyskinesia-in-parkinsons-disease/