A clinical and pharmacokinetic case study of an interaction of levodopa and antituberculous therapy in Parkinson's disease.
We studied the relationship between levodopa response and antituberculous treatment in a patient with idiopathic Parkinson's disease whose parkinsonism deteriorated when treatment with rifampicin and isoniazid (Rifinah) for pulmonary tuberculosis was started. A levodopa challenge test with regular recording of motor function was performed during, and again after stopping, antituberculous treatment. Plasma levodopa and levodopa metabolite pharmacokinetic profiles were determined using standard techniques. "On" period duration was 75% longer after antituberculous treatment had been stopped. These clinical findings correlated with a 37% increase in area under the concentration versus time curve (AUC), a 103% increase in apparent elimination half-life (t1/2), a 41% increase in time to maximum concentration (Tmax), and a 33% decrease in maximum concentration (Cmax) of levodopa. A concurrent increase in plasma 3-O-methyldopa (3-OMD) and a decrease in plasma 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the three major metabolites of levodopa, suggests an inhibition of the enzyme dopa decarboxylase, probably by isoniazid.
Wenning
G K
GK
University Department of Clinical Neurology, Institute of Neurology, London, England.
O'Connell
M T
MT
Patsalos
P N
PN
Quinn
N P
NP
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000995:Antitubercular Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004296:Dopa Decarboxylase / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D007538:Isoniazid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007980:Levodopa / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy*; D012293:Rifampin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000188:drug therapy
D000995:Antitubercular Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D004296:Dopa Decarboxylase; D007538:Isoniazid; D012293:Rifampin; D006719:Homovanillic Acid