Entacapone.
BACKGROUND
Levodopa (LD) is an efficient drug for patients with Parkinson's disease (PD). Its short half-life supports peaks and troughs. These plasma fluctuations support alternating stimulation of striatal postsynaptic dopamine receptors and thus onset of motor complications. They are significant components for the quality of treatment of PD patients.


METHODS
This review discusses peripheral components of motor complication manifestation related to LD metabolism.


RESULTS
LD troughs are associated with wearing off, which is reappearance of motor symptoms with decreasing drug effect. The addition of the catechol-O-methyltransferase inhibitor entacapone (EN) to LD/carbidopa (CD) improves wearing off, as EN prolongs LD half-life and avoids troughs. LD peaks are mostly related to peak dose dyskinesia, which are involuntary movements due to a central overstimulation with dopamine. One time addition of EN to LD/CD showed no increase of maximum LD concentration, but repeat EN supplementation to LD/CD elevated LD bioavailability and peaks.


CONCLUSIONS
These pharmacokinetic data may explain the failure of the STRIDE-PD study, which aimed to show a delayed interval of dyskinesia onset with LD/CD/EN therapy. This study only allowed up titration with a fixed LD intake every 4 h. But dyskinesia occurrence may require down titration of LD dose or delay of next LD intake.
Müller
Thomas
T
St. Joseph Hospital Berlin-Weissensee, Department of Neurology, Berlin, Germany. thomas.mueller@ruhr-uni-bochum.de
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D002230:Carbidopa / Q000008:administration & dosage; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009570:Nitriles / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology
D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D007980:Levodopa; C071192:entacapone; D002230:Carbidopa