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, activecontrolled, 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 C min , C max , C max −C min , AUC, t 1/2 , and t max .Results In healthy volunteers and PD patients, mean trough levels (C min ), C max , and AUC of levodopa were, in general, significantly higher during LCE compared to LC administration. Compared to C min , C max , and AUC, differences between the treatments in variability of levodopa concentrations (C max −C min ) 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.

Inhibition of catechol-O-methyltransferase modifies acute homocysteine rise during repeated levodopa application in patients with Parkinson’s disease

“…But this trial also shows a general tendency of homocysteine accumulation during repeated acute oral levodopa/DDI administration with and without EN over the threshold of 15 μmol/l within 2 days (Muller and Muhlack 2010). Expectedly, there was a general increase of levodopa plasma occurrence with additional EN application (Kuoppamaki et al 2009). Earlier investigations showed that less-pronounced troughs and higher C max of levodopa concentrations appear after addition of EN to levodopa/DDI Kuoppamaki et al 2009).…”

“…Expectedly, there was a general increase of levodopa plasma occurrence with additional EN application (Kuoppamaki et al 2009). Earlier investigations showed that less-pronounced troughs and higher C max of levodopa concentrations appear after addition of EN to levodopa/DDI Kuoppamaki et al 2009). We confirm that T max further goes up with EN supplementation in PD patients .…”

Pharmacokinetics of Levodopa, Carbidopa, and 3-O-Methyldopa Following 16-hour Jejunal Infusion of Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson’s Disease Patients

“…Currently available PD medications often result in significant variations in plasma levodopa levels (40)(41)(42), which may contribute to the motor fluctuations observed in advanced disease (43). Stable plasma levodopa concentrations during LCIG administration may result in more consistent dopaminergic stimulation in the brains of PD patients and subsequent improvement in clinical symptoms.…”

Use of Three-Component Levodopa (Levodopa/Carbidopa/Entacapone) to Correct Nocturnal Symptoms of Parkinson,s Disease

“…Проводимые в Центре экстрапирамидных заболе-ваний нервной системы открытое рандомизированное перекрестное исследование, посвященное изучению фармакокинетики однократной дозы леводопа / карби-допа / энтакапон 200 и леводопа / карбидопа контроли-руемого высвобождения 200, а также изучение эффек-тивности леводопа / карбидопа / энтакапон коррекции ночных симптомов БП при приеме однократной дозы перед сном показали статистически значимое сниже-ние выраженности симптомов БП, проявляющихся в ночное время [9][10][11][12].…”