High levodopa plasma concentration after oral administration predicts levodopa-induced dyskinesia in Parkinson's disease

Abstract

IntroductionIn patients with Parkinson's disease (PD), pulsatile dopaminergic stimulation may be a primary cause of levodopa-induced dyskinesia (LID). We aimed to investigate the correlation between levodopa pharmacokinetics (PK) and LID in PD. MethodsWe retrospectively reviewed the consecutive series of 255 PD patients without LID who underwent PK assessments with 100 mg levodopa. The type of peripheral decarboxylase inhibitor used in the PK assessments was determined by the usual prescription of the formulations of levodopa (10 mg carbidopa [n = 185] and 25 mg benserazide [n = 70]). ResultsDuring 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 symptoms (p = 0.009). In the multivariate Cox proportional hazards models, Cmax and AUC were associated with incident LID (Hazard Ratio [HR] 1.11, 95% confidence interval [CI] 1.03–1.19 and HR 1.13, 95% CI 1.03–1.24, respectively). In addition, younger age, benserazide use, LEDD, and MAOBI use were associated with incident LID. ConclusionHigh levodopa plasma concentration after oral administration was associated with incident LID in patients with PD.