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  • Title: The pharmacokinetic profile of the "first ever" oral dose of levodopa in de novo patients with Parkinson's disease.
    Author: Djaldetti R, Rosmarin V, Ziv I, Melamed E.
    Journal: Clin Neuropharmacol; 2001; 24(2):95-8. PubMed ID: 11307044.
    Abstract:
    To understand the delay in the clinical benefit that commonly occurs after initiation of levodopa (L-Dopa) treatment, we examined the pharmacokinetic profile of L-Dopa after the first oral dose ever taken of L-Dopa/carbidopa in untreated patients with Parkinson's disease and followed these parameters after 1 month of treatment. This was performed in correlation with the clinical therapeutic effect. Plasma levels of L-Dopa were measured with use of high-performance liquid chromatography with electrochemical detection after administration of the "first ever" 125 mg L-Dopa/12.5 mg carbidopa tablet in 15 patients with de novo Parkinson's disease (mean age, 69 +/- 11 y, mean disease duration, 1.5 +/- 0.8 years). Blood samples were drawn before administration and thereafter at various intervals for a period of 4 hours. Repeated measurements after the same oral dose were performed after 1 month of continued therapy with L-Dopa/carbidopa 125/12.5 mg three times daily. Patients were clinically evaluated by unified Parkinson's disease rating scale motor scores. There was a modest clinical improvement after 1 month of continuous L-Dopa treatment (motor scores, 13.1 +/- 11.6 vs. 17.6 +/- 11.7; p < 0.01). Peak plasma L-Dopa levels and area under the curve did not differ significantly between the first-ever dose and after 1 month of continuous treatment (0.9 +/- 0.1 vs. 1.0 +/- 0.1 microg/mL and 66.0 +/- 30.9 vs. 86.2 +/- 34.9 microg/mL, respectively; p < 0.1. There was also no change in time to peak levels between measurements. Results indicate that the first-ever dose of oral L-Dopa is well absorbed and that pharmacokinetic mechanisms such as reduced absorption of L-Dopa probably do not play a major role in the initial delay in clinical response to oral L-Dopa/carbidopa in patients with Parkinson's disease. The latter phenomena may be linked to central pharmacodynamic mechanisms.
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