Diurnal motor variations to repeated doses of levodopa in Parkinson's disease

Patients with Parkinson's disease (PD) in long-term levodopa therapy often complain of worsening of motor symptoms in the afternoon and evening. The p athophysiology of this phenomenon is not known. We evaluated the motor resp onse to repeated doses of levodopa during a 12-hour period in 52 parkinsoni an patients (19 de novo, 20 stable, and 13 wearing-off). On the day of the study, all patients received standard doses of levodopa/carbidopa at 8:00 a .m., 12:00 noon, and 4:00 p.m. Motor measurements such as lapping test, wal king time, and tremor score, and blood samples for levodopa and 3-O-methyld opa (30MD) plasma analysis, were performed hourly. Mean motor scores and ph armacokinetic data, evaluated for a period of 3 hours after each levodopa d ose, were compared. In de novo patients, we did not observe diurnal changes in motor score, whereas a progressive daytime worsening was visible in sta ble and wearing-off patients. No significant difference in levodopa pharmac okinetics after each levodopa dose was observed within each patient group, whereas 30MD plasma levels significantly increased with repeated levodopa a dministrations. However, no significant correlation between motor scores an d 30MD plasma levels was observed, suggesting that the diminishing motor re sponse to afternoon and evening doses of levodopa in patients in long-term levodopa therapy does nor relate to the pharmacokinetics of the drug. It is possible that this phenomenon may be an expression of the occurrence of to lerance to repeated doses of levodopa.