Lack of pharmacokinetic interaction between the selective dopamine agonist cabergoline and the MAO-B inhibitor selegiline.
The addition of a dopamine agonist and of a monoamine oxidase type B inhibitor to I-dopa has been suggested in the therapy of Parkinson's disease. The plasma pharmacokinetics of both cabergoline and I-dopa have previously been shown to remain unaffected when the two drugs are given concomitantly. This study aimed at examining whether the plasma pharmacokinetic parameters of cabergoline and selegiline are modified when given in combination. Selegiline is hardly detectable in plasma. Therefore, the plasma levels of its metabolites amphetamine, methamphetamine and desmetylselegiline were used to assess the effect of cabergoline co-administration. Plasma levels of the selegiline metabolites were determined first after selegiline administration (10 mg/day) for 8 days, and then after administration of both drugs for 22 additional days (day 30). Cabergoline plasma levels were measured on day 30, and then after administration of cabergoline (1 mg/day) alone for further 22 days. No statistical difference was found between the Cmax.ss, tmax.ss, AUC0-24h.ss, C0h.ss, C24h.ss values of cabergoline and of the selegiline metabolites when the two drugs were given alone or in combination, indicating the absence of pharmacokinetic interaction between cabergoline and selegiline.
Dostert
P
P
1Pharmacia, Department of Pharmacokinetics and Metabolism, Milan, Italy.
Strolin Benedetti
M
M
Persiani
S
S
La Croix
R
R
Bosc
M
M
Fiorentini
F
F
Deffond
D
D
Vernay
D
D
Dordain
G
G
D000368:Aged; D000661:Amphetamine / Q000097:blood; D000662:Amphetamines / Q000097:blood; D000978:Antiparkinson Agents / Q000097:blood / Q000493:pharmacokinetics*; D000077465:Cabergoline; D018491:Dopamine Agonists / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004873:Ergolines / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000097:blood; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D012642:Selegiline / Q000493:pharmacokinetics*
D000662:Amphetamines; D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D004873:Ergolines; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D008694:Methamphetamine; C017861:desmethylselegiline; D000661:Amphetamine; D000077465:Cabergoline