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.