Delayed early morning turn “ON” in response to a single dose of levodopa in advanced Parkinson’s disease: pharmacokinetics should be considered
- 1Movement Disorders Unit, Service of Neurology and Neurosurgery, DIPRECA Hospital, Universidad de Santiago de Chile, Chile
- 2Neurosciences Unit, Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Chile
- Correspondence to: Dr P Chaná Universidad de Santiago de Chile, Belisario Prats 1597B, Santiago, Chile;
The pathophysiology underlying the fluctuations in response following oral levodopa therapy is complex and includes peripheral and central factors. The short half-life of levodopa, erratic gastrointestinal absorption, and competitive transport across the blood–brain barrier have been regarded as factors responsible for the fluctuating plasma and striatal concentrations of levodopa. Indeed, failure of an oral dose to produce an effect or delay in the onset of action have been associated with problems in absorption.1,2
We studied the pharmacokinetics of levodopa in 19 patients with advanced Parkinson’s disease (12 men, seven women; period of evolution of illness more than 10 years) with and without a delayed response to the first drug dose in the morning (delayed early morning turn “ON”). The patients were selected according to the UK Brain Bank criteria; those who could not tolerate an assessment after 12 hours without taking their antiparkinsonian medication were excluded. All patients signed an informed consent form before being included in the study.
Medication and food were withheld after midnight the night before the study day. All patients’ regular therapeutic first (morning) levodopa/carbidopa dose was between 125 mg and 250 mg. Therefore all patients received a single oral dose of levodopa/carbidopa (250/25 mg) at 9:00 am, to ensure that all had a response. …