Induction of aromatic‐l‐amino acid decarboxylase by decarboxylase inhibitors in idiopathic parkinsonism

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Abstract
We evaluated the effect of administration of L‐dopa, alone or in combination with a peripheral decarboxylase inhibitor, on plasma levels of aromatic‐L‐amino acid decarboxylase (ALAAD). After single‐dose administration of L‐dopa plus benserazide (Madopar) in healthy subjects and in chronically treated patients with parkinsonism, plasma ALAAD followed for 2 to 3 hours fell, but returned to predosing levels within 90 minutes. Four groups of patients with idiopathic parkinsonism were studied during chronic treatment: Group I, no L‐dopa treatment (n = 31); Group II, L‐dopa alone (n = 15); Group III, L‐dopa plus benserazide (n = 28); and Group IV, L‐dopa plus carbidopa (Sinemet, n = 30). Plasma ALAAD 2 hours after dosing was normal in Groups I and II. ALAAD was increased threefold in Groups III and IV, suggesting induction of ALAAD by the coad‐ministration of a peripheral decarboxylase inhibitor. In a study of 3 patients in whom L‐dopa/benserazide was started, plasma ALAAD rose gradually over 3 to 4 weeks. Further detailed pharmacokinetic studies of L‐dopa, dopamine, and ALAAD in plasma and cerebrospinal fluid are required to determine if the apparent ALAAD induction by a peripheral decarboxylase inhibitor 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.