Body Weight Influences Pharmacokinetics of Levodopa in Parkinson's Disease

Abstract

Changes in body weight may induce substantial variations in peripheral pharmacokinetics of drugs, but the relation between body weight and levodopa (LD) pharmacokinetics has never been investigated in Parkinson's disease. To address this issue, we conducted a pharmacokinetic study with 164 patients with sporadic Parkinson's disease. Patients underwent an oral acute LD test with 250 mg of LD, and pharmacokinetic variables were assessed at baseline and at 30, 60, 120, and 240 minutes after LD administration. Plasmatic-LD areas under the curve and body weight were significantly and inversely correlated as well as the elimination of the half-life of LD and body weight. In our sample, women were significantly lighter and had a significantly greater area under the curve than men. Moreover, a greater percentage of women showed LD peak-dose dyskinesias compared with men. Our findings suggest that lighter patients with Parkinson's disease probably receive a greater cumulative dosage of LD per kilogram of body weight during long-term treatment, because in clinical practice, LD is administered without any adjustment of the dose to body weight. This could explain gender differences for the development of LD-induced peak-dose dyskinesias observed during the course of the disease.

Gender differences in motor and non-motor symptoms among Sardinian patients with Parkinson's disease

“…The predominance of males in the present research is quite correspondent to other large clinical cohorts [34][35][36][37][38][39][40]. With regard to clinical characteristic of motor symptoms, we found that women are more likely than men to present with tremor as initial symptom.…”

The modern pre-levodopa era of Parkinson's disease: insights into motor complications from sub-Saharan Africa

“…In contrast with past drug trials, recent experimental studies suggest that the best therapeutic option to delay the molecular changes in gene expression, synaptic morphology and abnormal corticostriatal connectivity associated with dyskinesias may be early initiation of levodopa treatment (Marin et al , 2009). We emphasize the importance of considering the pharmacokinetic properties of levodopa and recommend (i) to adjust the individual levodopa dose regimen per kilogram of body weight to reduce the risk of dyskinesias (Zappia et al , 2002; Sharma et al , 2008; Olanow et al , 2013); and (ii) to consider the potential benefits of dietary protein redistribution during the daytime to minimize levodopa requirement and improve the control of motor fluctuations (Mena and Cotzias, 1975; Cereda et al , 2010). Further studies are needed to better understand the natural course of Parkinson’s disease without the confounding effect of medications, and the pathophysiology of motor and non-motor symptoms.…”

Neurotrophic and neuroprotective actions of estrogen: Basic mechanisms and clinical implications

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