Comparison of pharmacokinetic profile of levodopa throughout the day between levodopa/carbidopa/entacapone and levodopa/carbidopa when administered four or five times daily

• Published in: European journal of clinical pharmacology 2009-05, Vol.65 (5), p.443-455
• Main Authors: Kuoppamäki, Mikko, Korpela, Kirsi, Marttila, Reijo, Kaasinen, Valtteri, Hartikainen, Päivi, Lyytinen, Jukka, Kaakkola, Seppo, Hänninen, Jutta, Löyttyniemi, Eliisa, Kailajärvi, Marita, Ruokoniemi, Päivi, Ellmén, Juha
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adolescent; Adult; Antiparkinson Agents - administration & dosage; Antiparkinson Agents - blood; Antiparkinson Agents - pharmacokinetics; Area Under Curve; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Carbidopa; Carbidopa - administration & dosage; Carbidopa - blood; Carbidopa - pharmacokinetics; Case-Control Studies; Catechol O-Methyltransferase - metabolism; Catechol O-Methyltransferase Inhibitors; Catechols - administration & dosage; Catechols - blood; Catechols - pharmacokinetics; Clinical outcomes; Clinical Trial; Clinical trials; Comparative studies; Cross-Over Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Entacapone; Female; Half-Life; Humans; L-dopa; Levodopa - administration & dosage; Levodopa - blood; Levodopa - pharmacokinetics; Male; Medical sciences; Metabolic Clearance Rate; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Nitriles - administration & dosage; Nitriles - blood; Nitriles - pharmacokinetics; Parkinson disease; Parkinsons disease; pharmacokinetics; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Prescription drugs; Young Adult
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-009-0622-y

Objectives To compare plasma levodopa concentrations after repeated doses of levodopa/carbidopa/entacapone (LCE) and levodopa/carbidopa (LC). Methods Open-label, randomized, two-period, active-controlled, cross-over study with four dosing regimens: groups I and II (healthy volunteers and Parkinson's disease patients) received levodopa 100 mg or 150 mg four times daily, respectively, and groups III and IV (healthy volunteers) received the same strengths of levodopa five times daily. Pharmacokinetic (PK) parameters determined for levodopa included Cmin, Cmax, Cmax - Cmin, AUC, t₁/₂, and tmax. Results In healthy volunteers and PD patients, mean trough levels (Cmin), Cmax, and AUC of levodopa were, in general, significantly higher during LCE compared to LC administration. Compared to Cmin, Cmax, and AUC, differences between the treatments in variability of levodopa concentrations (Cmax - Cmin) were less consistent. Conclusions The present results on the differences in levodopa PK between LCE and LC provide a basis to evaluate the relationship of levodopa PK and the induction of motor complications in an on-going study in early Parkinson's disease using similar dosing regimens.