, Volume 65, Issue 5, pp 443-455,
Open Access This content is freely available online to anyone, anywhere at any time.
Date: 20 Feb 2009

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

Abstract

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.

Marita Kailajärvi and Päivi Ruokoniemi were employed by CRST, University of Turku. Orion Corporation Orion Pharma was the sponsor of the study and paid compensation to CRST. Jutta Hänninen, Kirsi Korpela, Eliisa Löyttyniemi, Mikko Kuoppamäki and Juha Ellmén are employees of Orion Corporation Orion Pharma.