Treatment of idiopathic parkinsonism with L-dopa in the absence and presence of decarboxylase inhibitors: effects on plasma levels of L-dopa, dopa decarboxylase, catecholamines and 3-O-methyl-dopa.

Abstract

The effect of levodopa (L-dopa), alone or in combination with a peripheral decarboxylase inhibitor (PDI), on plasma levels of aromatic-L-amino acid decarboxylase (ALAAD, = dopa decarboxylase), L-dopa, 3-O-methyl-dopa (3-OMD), dopamine (DA), noradrenaline, adrenaline and dopamine beta-hydroxylase has been studied. In healthy subjects and in patients with parkinsonism plasma ALAAD level fell after administration of L-dopa + benserazide, but returned to previous levels within 90 min. In a cross-sectional study blood was obtained, 2 h after dosing, from 104 patients with idiopathic parkinsonism, divided into four groups: no L-dopa treatment (group 1), L-dopa alone (group 2), L-dopa + benserazide (Madopar) (group 3) and L-dopa + carbidopa (Sinemet) (group 4). Plasma ALAAD, which was normal in groups 1 and 2, was increased 3-fold in groups 3 and 4, indicating that there was induction of ALAAD by the co-administration of PDI. Despite this induction of ALAAD, in groups 3 and 4, with half the daily L-dopa dose compared with group 2, plasma L-dopa and 3-OMD levels were 5 times higher, while plasma DA levels were not different. The DA/L-dopa ratio was decreased 5-fold in group 2 and 16-fold in groups 3 and 4 as compared with group 1. Neither 3-OMD levels nor 3-OMD/L-dopa ratios correlated with the occurrence of on-off fluctuations. In a longitudinal study of three patients started on Madopar treatment the induction of plasma ALAAD was found to occur gradually over 3-4 weeks. Further detailed pharmacokinetic studies in plasma and cerebrospinal fluid are required in order to elucidate whether the ALAAD induction by PDI may be related to the loss of clinical efficacy of combination therapy in some patients and how it is related to end-of-dose deterioration and on-off phenomena.

• Authors: F Boomsma, J D Meerwaldt, A J Man in't Veld, A Hovestadt, M A Schalekamp
• Journal: Journal of neurology (J Neurol) Vol. 236 Issue 4 Pg. 223-30 (May 1989) ISSN: 0340-5354 [Print] Germany
• PMID: 2760634 (Publication Type: Journal Article)

Chemical References

• Catecholamines
• Drug Combinations
• benserazide, levodopa drug combination
• Tyrosine
• Levodopa
• Phenytoin
• Benserazide
• Carboxy-Lyases
• Dopa Decarboxylase
• 3-methoxytyrosine

Topics

• Administration, Oral
• Aged
• Benserazide (blood, pharmacokinetics, therapeutic use)
• Carboxy-Lyases (administration & dosage, antagonists & inhibitors, blood, therapeutic use)
• Catecholamines (blood)
• Dopa Decarboxylase (blood)
• Drug Combinations (blood, pharmacokinetics, therapeutic use)
• Drug Therapy, Combination
• Female
• Humans
• Levodopa (blood, pharmacokinetics, therapeutic use)
• Longitudinal Studies
• Male
• Middle Aged
• Parkinson Disease (drug therapy)
• Phenytoin (pharmacokinetics, therapeutic use)
• Time Factors
• Tyrosine (analogs & derivatives, blood)