COMT inhibition with tolcapone does not affect carbidopa pharmacokinetics in parkinsonian patients in levodopa/carbidopa (Sinemet).
OBJECTIVE
Tolcapone is a novel catechol-O-methyltransferase (COMT) inhibitor used as an adjunct to levodopa/carbidopa or levodopa/benserazide therapy to improve treatment of Parkinson's disease. The aim of the current study was to investigate the potential effect of tolcapone on the pharmacokinetics of carbidopa.


METHODS
This was an open-label study in 12 parkinsonian patients receiving optimal levodopa/carbidopa therapy and tolcapone 200 mg three times daily for 6 weeks. Blood samples were taken at baseline (i.e. before the first tolcapone intake) and after 1-2 weeks and 6 weeks so that carbidopa pharmacokinetics before and during tolcapone treatment could be assessed.


RESULTS
No changes in any pharmacokinetic parameters of carbidopa were observed. The mean AUC(0,tau) and Cmax values at baseline were 0.39 microg ml-1 h and 0. 14 microg ml-1, respectively. During tolcapone treatment these values were on average 0.35 microg ml-1 h (AUC(0,tau), week 1-2), 0. 34 microg ml-1 h (AUC(0,tau), week 6 and 0.13 microg ml-1 (Cmax, weeks 1-2 and 6). tmax remained unchanged (approx. 2 h).


CONCLUSIONS
These results indicate that tolcapone does not affect carbidopa elimination and that no interaction of any clinical relevance occurs between tolcapone and carbidopa.
Jorga
K M
KM
Department of Clinical Pharmacology, F. Hoffmann-La Roche Ltd, Basel, Switzerland. karin.jorga@roche.com
Nicholl
D J
DJ
D000368:Aged; D000978:Antiparkinson Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001577:Benzophenones / Q000494:pharmacology*; D002230:Carbidopa / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D004338:Drug Combinations; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009596:Nitrophenols; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D000077867:Tolcapone
D000978:Antiparkinson Agents; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D009596:Nitrophenols; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D000077867:Tolcapone; D002394:Catechol O-Methyltransferase; D002230:Carbidopa