title: The pharmacokinetic profile of the "first ever" oral dose of levodopa in de novo patients with Parkinson's disease.
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.
authors: Department of Neurology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel.
authors: R
authors: R
authors: Djaldetti
authors: V
authors: V
authors: Rosmarin
authors: I
authors: I
authors: Ziv
authors: E
authors: E
authors: Melamed
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood* / Q000188:drug therapy
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa