Individualization of Levodopa Therapy

Bianchine, Joseph R.; Sunyapridakul, Laddawan

doi:10.1016/s0025-7125(16)32103-4

Cited by 7 publications

(2 citation statements)

References 39 publications

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“…The importance of individualizing therapy in Parkinson's disease has been well established [61]. The large number of variables which affect final dopamine concentration at receptor sites in the striatum necessitate to move to an individualized dosing approach.…”

Section: Resultsmentioning

confidence: 99%

Levodopa in Parkinson’s Disease: A Review of Population Pharmacokinetics/Pharmacodynamics Analysis

et al. 2017

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-Background:Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. Although levodopa remains the single effective agent in the management of Parkinson's disease, the accurate determination of this optimal dosage is complicated by marked betweensubject and between-occasion variability in this population. This review presents a synthesis of the population pharmacokinetic and pharmacodynamic models of levodopa described in Parkinson's disease. METHODS: A literature search was conducted from the PubMed database, from their inception through April 2016, using the following terms: levodopa, pharmacokinetic(s), pharmacodynamic(s) population, model(ling) and nonlinear mixed effect. Articles were excluded if they were not pertinent. References of all selected articles were also evaluated. RESULTS: A total of 12 articles were finally retained. The following covariates were selected as interindividual variability factors: body weight, age, sex, creatinine clearance and levodopa dose. The clinical response versus effect site concentration relationship was described with different sigmoidal Emax models. Different pharmacodynamic effects were described: UPDRS, Tapping, Dyskinesia, CURSΣ and treatment response scale. DISCUSSION: This review allows us to realize interpretation of a patient's clinical picture and confirmed the appropriateness of the pharmacokinetic-pharmacodynamic modeling for levodopa. External evaluation of previous published models should be also continued to evaluate these previous studies. New pharmacokinetic and/or pharmacodynamic population modelling studies could be consider to improve future models and decrease variability, to better understand the evolution of patients with Parkinson's disease treated by levodopa.

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Section: Resultsmentioning

confidence: 99%

Levodopa in Parkinson’s Disease: A Review of Population Pharmacokinetics/Pharmacodynamics Analysis

et al. 2017

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“…Different dose requirements among elderly parkinsonian patients from those in the other age-groups (Broe & Caird 1973;Vignalou & Beck 1973;Grad et a1 1974) might be indicative of either variability in the systemic availability or changes in the elimination kinetics of levodopa. A 'tailor-made' dosage regimen for each patient has therefore been characteristic of levodopa therapy (Bianchine & Sunyapridakul 1974). Evans et a1 (1980) reported that the area under the plasma levodopa concentration-time curve in elderly parkinsonian patients (X 77 years) was significantly larger than that in young healthy volunteers (X 26 years) despite the same elimination half-life in both groups.…”

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confidence: 99%

Effect of age on gastrointestinal and hepatic first-pass effects of levodopa in rats

Iwamoto

Watanabe

Yamada

et al. 1987

Journal of Pharmacy and Pharmacology

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Presystemic elimination of levodopa (20 mg kg-1) has been studied in 5- to 104-week-old male Wistar rats. The gastrointestinal and hepatic contribution to the overall first-pass effect was estimated separately after the drug had been administered intravenously, orally and intraportally. The contribution of the gut to the overall first-pass effect of this drug was greater than that of the liver in any age-group of the rats. Both the overall and intestinal first-pass effects of levodopa were greatest in 11-week-old rats and relatively small in both young (between weeks 5 and 7) and aged (between weeks 52 and 104) rats. In contrast, the hepatic first-pass effect did not show any significant age-dependent change. Age-related change in the jejunal blood flow could not explain the unique age-dependence in the intestinal first-pass metabolism of levodopa. However, the present age-dependence in the oral systemic availability of this drug between adult (11 weeks) and aged (52 to 104 weeks) rats was found to be similar to the tendency that has been reported between normal adult subjects and aged patients with Parkinson's disease.

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Parkinson's disease, melanoma, and levodopa

Fermaglich

Delaney

1977

J. Neurol.

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Individualization of Levodopa Therapy

Cited by 7 publications

References 39 publications

Levodopa in Parkinson’s Disease: A Review of Population Pharmacokinetics/Pharmacodynamics Analysis

Levodopa in Parkinson’s Disease: A Review of Population Pharmacokinetics/Pharmacodynamics Analysis

Effect of age on gastrointestinal and hepatic first-pass effects of levodopa in rats

Parkinson's disease, melanoma, and levodopa

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