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Levodopa/carbidopa microtablets in Parkinson’s disease: a study of pharmacokinetics and blinded motor assessment

Artikel i vetenskaplig tidskrift
Författare Marina Senek
Sten Magnus Aquilonius
Håkan Askmark
Filip Bergquist
Radu Constantinescu
Anders Ericsson
Sara Lycke
Alexander Medvedev
Mevludin Memedi
Fredrik Ohlsson
Jack Spira
Jerker Westin
Dag Nyholm
Publicerad i European Journal of Pharmacology
Volym 73
Sidor 563-571
ISSN 0014-2999
Publiceringsår 2017
Publicerad vid Institutionen för neurovetenskap och fysiologi
Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi
Sidor 563-571
Språk en
Länkar dx.doi.org/10.1007/s00228-017-2196-...
https://gup.ub.gu.se/file/206902
Ämnesord Levodopa, Parkinson’s disease, Pharmacodynamics, Pharmacokinetics
Ämneskategorier Neurovetenskaper, Farmakologi och toxikologi, Neurologi

Sammanfattning

Motor function assessments with rating scales in relation to the pharmacokinetics of levodopa may increase the understanding of how to individualize and fine-tune treatments. Objectives: This study aimed to investigate the pharmacokinetic profiles of levodopa-carbidopa and the motor function following a single-dose microtablet administration in Parkinson’s disease. Methods: This was a single-center, open-label, single-dose study in 19 patients experiencing motor fluctuations. Patients received 150% of their individual levodopa equivalent morning dose in levodopa-carbidopa microtablets. Blood samples were collected at pre-specified time points. Patients were video recorded and motor function was assessed with six UPDRS part III motor items, dyskinesia score, and the treatment response scale (TRS), rated by three blinded movement disorder specialists. Results: AUC0–4/dose and Cmax/dose for levodopa was found to be higher in Parkinson’s disease patients compared with healthy subjects from a previous study, (p = 0.0008 and p = 0.026, respectively). The mean time to maximum improvement in sum of six UPDRS items score was 78 min (±59) (n = 16), and the mean time to TRS score maximum effect was 54 min (±51) (n = 15). Mean time to onset of dyskinesia was 41 min (±38) (n = 13). Conclusions: In the PD population, following levodopa/carbidopa microtablet administration in fasting state, the Cmax and AUC0–4/dose were found to be higher compared with results from a previous study in young, healthy subjects. A large between subject variability in response and duration of effect was observed, highlighting the importance of a continuous and individual assessment of motor function in order to optimize treatment effect.

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