Fewer fluctuations, higher maximum concentration and better motor response of levodopa with catechol-O-methyltransferase inhibition.
Catechol-O-methyltransferase inhibitor addition to levodopa/carbidopa formulations improves motor symptoms and reduces levodopa fluctuations in patients with Parkinson's disease. Objectives were to investigate the effects of entacapone and tolcapone on plasma behaviour of levodopa, its metabolite 3-O-methyldopa and on motor impairment. 22 patients orally received levodopa/carbidopa first, then levodopa/carbidopa/entacapone and finally levodopa/carbidopa plus tolcapone within a 4.5 h interval twice. Maximum concentration, time to maximum level and bioavailability of levodopa did not differ between all conditions each with 200 mg levodopa application as a whole. Catechol-O-methyltransferase inhibition caused less fluctuations and higher baseline levels of levodopa after the first intake and less 3-O-methyldopa appearance. The maximum levodopa concentrations were higher after the second levodopa intake, particularly with catechol-O-methyltransferase inhibition. The motor response to levodopa was better with catechol-O-methyltransferase inhibition than without, tolcapone was superior to entacapone. More continuous levodopa brain delivery and lower 3-O-methyldopa bioavailability caused a better motor response during catechol-O-methyltransferase inhibition.
Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany.
Siegfried
S
Muhlack
Lennard
L
Herrmann
Stephan
S
Salmen
Thomas
T
Müller
D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D001577:Benzophenones / Q000097:blood / Q000627:therapeutic use; D002230:Carbidopa / Q000627:therapeutic use; D065098:Catechol O-Methyltransferase Inhibitors / Q000097:blood / Q000627:therapeutic use*; D002396:Catechols / Q000097:blood / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects*; D009570:Nitriles / Q000097:blood / Q000627:therapeutic use; D009596:Nitrophenols / Q000097:blood / Q000627:therapeutic use; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D011597:Psychomotor Performance / Q000187:drug effects*; D018709:Statistics, Nonparametric; D000077867:Tolcapone; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D009570:Nitriles; D009596:Nitrophenols; D007980:Levodopa; C071192:entacapone; D000077867:Tolcapone; D002230:Carbidopa