Effect of clarithromycin on the pharmacokinetics of cabergoline in healthy controls and in patients with Parkinson's disease.
Cabergoline is used in the treatment of Parkinson's disease (PD). Clarithromycin is a potent inhibitor of CYP3A4 and P-glycoprotein and is often co-administered with cabergoline in usual clinical practice. We studied the effect of clarithromycin co-administration on the blood concentration of cabergoline in healthy male volunteers and in PD patients. Study 1: Ten healthy male volunteers were enrolled and were randomized to take a single oral dose of cabergoline (1 mg/day) for 6 days or a single oral dose of cabergoline plus clarithromycin (400 mg/day) for 6 days. Study 2: Seven PD patients receiving stable cabergoline doses were enrolled. They were evaluated for the plasma cabergoline concentration before and after the addition of clarithromycin 400 mg/day for 6 days, and again 1 month after discontinuation of clarithromycin. The dose and duration of clarithromycin were decided according to usual clinical practice. In healthy male volunteers, mean Cmax and AUC(0-10 h) of cabergoline increased to a similar degree during co-administration of clarithromycin. Mean plasma cabergoline concentration over 10 h post-dosing increased 2.6-fold with clarithromycin co-administration. In PD patients, plasma cabergoline concentration increased 1.7-fold during clarithromycin co-administration. Co-administration with clarithromycin may increase the blood concentration of cabergoline in healthy volunteers and in PD patients.
Nakatsuka
Akiko
A
Clinical Pharmacology and Therapeutics, Ehime University School of Medicine, Ehime University Hospital, Shitsukawa Tohon, Ehime, Japan.
Nagai
Masahiro
M
Yabe
Hayato
H
Nishikawa
Noriko
N
Nomura
Takuo
T
Moritoyo
Hiroyoko
H
Moritoyo
Takashi
T
Nomoto
Masahiro
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000077465:Cabergoline; D017291:Clarithromycin / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D004347:Drug Interactions; D004873:Ergolines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000900:Anti-Bacterial Agents; D018491:Dopamine Agonists; D004873:Ergolines; D017291:Clarithromycin; D000077465:Cabergoline