Induction of aromatic-L-amino acid decarboxylase by decarboxylase inhibitors in idiopathic parkinsonism.
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 coadministration 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.
Boomsma
F
F
Department of Internal Medicine I, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.
Meerwaldt
J D
JD
Man in 't Veld
A J
AJ
Hovestadt
A
A
Schalekamp
M A
MA
D000368:Aged; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000096:biosynthesis* / Q000097:blood; D001545:Benserazide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D002262:Carboxy-Lyases / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000097:blood / Q000493:pharmacokinetics; D004338:Drug Combinations / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism; D013997:Time Factors
D004338:Drug Combinations; C005177:benserazide, levodopa drug combination; D007980:Levodopa; D001545:Benserazide; D002262:Carboxy-Lyases; D001142:Aromatic-L-Amino-Acid Decarboxylases