The effect of erythromycin on the pharmacokinetics and pharmacodynamics of zopiclone.
1. The effect of erythromycin on the pharmacokinetics and pharmacodynamics of oral zopiclone, a non-benzodiazepine hypnotic, was investigated in a double-blind, cross-over study. 2. Ten healthy volunteers were given placebo or 500 mg erythromycin orally three times a day for 6 days followed by an oral dose of 7.5 mg zopiclone. 3. Erythromycin increased plasma zopiclone concentration by 4-fold at 0.5 h (P < 0.05) and by 2-fold at 1 h (P < 0.05). There were increases of 3- and 2-fold in the AUC(0,1 h) and AUC(0,2 h) values (P < 0.05). The total AUC of zopiclone increased by 80% (P < 0.05) but the peak concentration by only 40% (P < 0.05). The peak time of zopiclone concentration was reduced from 2 to 1 h (P < 0.001). 4. Significant pharmacodynamic differences between the treatments were observed from 0.5 h to 2 h with respect to saccadic latency and digit symbol substitution tests. 5. The interaction between erythromycin and zopiclone resulted mainly in accelerated absorption which may lead to a faster hypnotic effect in patients.
Department of Clinical Pharmacology, University of Helsinki, Finland.
K
K
Aranko
H
H
Luurila
J T
JT
Backman
P J
PJ
Neuvonen
K T
KT
Olkkola
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D053961:Azabicyclo Compounds; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D004917:Erythromycin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*
D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone; D004917:Erythromycin