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

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&#...

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Vydané v:	European journal of clinical pharmacology Ročník 65; číslo 5; s. 443 - 455
Hlavní autori:	Kuoppamäki, Mikko, Korpela, Kirsi, Marttila, Reijo, Kaasinen, Valtteri, Hartikainen, Päivi, Lyytinen, Jukka, Kaakkola, Seppo, Hänninen, Jutta, Löyttyniemi, Eliisa, Kailajärvi, Marita, Ruokoniemi, Päivi, Ellmén, Juha
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.05.2009 Springer-Verlag Springer Springer Nature B.V Springer Verlag
Predmet:	administration & dosage Administration, Oral Adolescent Adult Antiparkinson Agents Antiparkinson Agents - administration & dosage Antiparkinson Agents - blood Antiparkinson Agents - pharmacokinetics Area Under Curve Biological and medical sciences Biomedical and Life Sciences Biomedicine blood Carbidopa Carbidopa - administration & dosage Carbidopa - blood Carbidopa - pharmacokinetics Case-Control Studies Catechol O-Methyltransferase Catechol O-Methyltransferase - metabolism Catechol O-Methyltransferase Inhibitors Catechols 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 Levodopa - administration & dosage Levodopa - blood Levodopa - pharmacokinetics Male Medical sciences Metabolic Clearance Rate metabolism Nervous system (semeiology, syndromes) Nervous system as a whole Neurology Nitriles Nitriles - administration & dosage Nitriles - blood Nitriles - pharmacokinetics Parkinson disease Parkinsons disease pharmacokinetics Pharmacology Pharmacology. Drug treatments Pharmacology/Toxicology Prescription drugs Young Adult Entacapone Levodopa Carbidopa Pharmacokinetics Parkinson’s disease Agonist Parkinson's disease Parkinson disease Catechol O-methyltransferase Lyases Carboxy-lyases Degenerative disease Human Decarboxylase Nervous system diseases Enzyme Transferases Enzyme inhibitor Antiparkinson agent Cerebral disorder Carbon-carbon lyases D2 Dopamine receptor Methyltransferases Central nervous system disease Comparative study Extrapyramidal syndrome
ISSN:	0031-6970, 1432-1041, 1432-1041
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Shrnutí:	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.
Bibliografia:	http://dx.doi.org/10.1007/s00228-009-0622-y ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	0031-6970 1432-1041 1432-1041
DOI:	10.1007/s00228-009-0622-y