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

• Published in: European journal of clinical pharmacology Vol. 73; no. 5; pp. 563 - 571
• Main Authors: Senek, Marina, Aquilonius, Sten-Magnus, Askmark, Håkan, Bergquist, Filip, Constantinescu, Radu, Ericsson, Anders, Lycke, Sara, Medvedev, Alexander, Memedi, Mevludin, Ohlsson, Fredrik, Spira, Jack, Westin, Jerker, Nyholm, Dag
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2017; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Antiparkinson Agents - administration & dosage; Antiparkinson Agents - therapeutic use; Area Under Curve; Biomedical and Life Sciences; Biomedicine; Carbidopa - administration & dosage; Carbidopa - therapeutic use; Complex Systems – Microdata Analysis; Farmakologi och toxikologi; Female; Humans; Informatics; Informatik; Kinetics; Komplexa system - mikrodataanalys; Levodopa; Levodopa - administration & dosage; Levodopa - therapeutic use; Male; Middle Aged; Motor Activity; Neurologi; Neurology; Neurosciences; Neurovetenskaper; Parkinson Disease - drug therapy; Parkinson Disease - physiopathology; Parkinson's disease; Pharmacodynamics; Pharmacokinetics; Pharmacokinetics and Disposition; Pharmacology; Pharmacology and Toxicology; Pharmacology/Toxicology; Prescription drugs; Tablets; Pharmacodynamics; Levodopa; Pharmacokinetics; Parkinson’s disease
• ISSN: 0031-6970; 1432-1041; 0014-2999; 1432-1041
• DOI: 10.1007/s00228-017-2196-4

Background 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 AUC 0–4/dose and C max/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 C max and AUC 0–4/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.