Levodopa/carbidopa/entacapone combination in chronotherapy of Parkinson’s disease

Objective. To evaluate the efficacy of the levodopa/carbidopa/entacapone combination in the chronotherapy of Parkinson’s disease (PD). Material and methods. This multicenter study was conducted at seven clinical sites, with 72 patients completing the follow-up period. The efficacy of levodopa/carbidopa/entacapone administration was evaluated in relation to the daily activity profile of levodopa. Patients recorded hourly assessments of «on», «off», and dyskinesia periods in a diary before and after therapy adjustment. The follow-up period lasted one month. Results. Patients misidentified «on» periods in 46% of cases and «off» periods in 35% of cases. The daily profile of levodopa efficacy was heterogeneous: the favorable period occurred in the morning for 40% of patients, in the afternoon for 32%, in the evening for 21%, and in the late evening for 7%. Tailoring levodopa/carbidopa/entacapone administration to the circadian profile improved outcomes in 72% of patients. A morning peak in efficacy predicted high drug sensitivity, while shifting the favorable period to the evening was associated with lower therapy efficacy. Conclusions. Optimizing the timing of antiparkinsonian drug administration in accordance with the circadian rhythm of PD symptoms may enhance therapeutic efficacy. Chronotherapy that incorporates the circadian profile of levodopa efficacy can maximize the benefits of levodopa/carbidopa/entacapone combination therapy.