Comparison of pharmacokinetic profile of levodopa throughout the day between levodopa/carbidopa/entacapone and levodopa/carbidopa when administered four or five times daily.
OBJECTIVE
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, t(1/2), 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.
Kuoppamäki
Mikko
M
Orion Pharma, Clinical R&D, CNS, P.O. Box 425, Turku 20101, Finland. mikko.kuoppamaki@orionpharma.com
Korpela
Kirsi
K
Marttila
Reijo
R
Kaasinen
Valtteri
V
Hartikainen
Päivi
P
Lyytinen
Jukka
J
Kaakkola
Seppo
S
Hänninen
Jutta
J
Löyttyniemi
Eliisa
E
Kailajärvi
Marita
M
Ruokoniemi
Päivi
P
Ellmén
Juha
J
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002230:Carbidopa / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D009570:Nitriles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004338:Drug Combinations; D009570:Nitriles; D007980:Levodopa; C071192:entacapone; D002394:Catechol O-Methyltransferase; D002230:Carbidopa