Actions of zopiclone and carbamazepine, alone and in combination, on human skilled performance in laboratory and clinical tests.
1. Possible interactions of zopiclone and carbamazepine on human skilled performance were studied in a randomized, double-blind, crossover trial with 12 healthy young subjects. 2. Psychomotor performance (coordination, reactions, attention, cognition) and subjective effects (VAS) were measured and venous blood sampled before and 1.5, 3, 4.5 and 6 h after single oral doses of placebo, 7.5 mg of zopiclone and 600 mg of carbamazepine, which were given alone or combined. Clinical test for drunkenness (CTD) was done 2 and 5 h after drug intake. 3. Both zopiclone and carbamazepine, when administered alone, impaired performance on laboratory tests, the decrements being recorded 1.5 to 6 h after intake. In line with the plasma concentrations, the zopiclone effects peaked earlier (at 1.5 h) and lasted for a shorter time than those of carbamazepine. Zopiclone had a more pronounced effect on perceptual and cognitive functions (digit substitution) and it affected extraocular muscle tone (Maddox wing), whereas carbamazepine had stronger effects on attention. Additive pharmacodynamic actions were found in most tests after the combined treatment with zopiclone and carbamazepine. 4. CTD proved to be less sensitive than the laboratory tests in revealing drug-induced decrement of performance after administration of one agent alone. However, it revealed the combined decremental effects of zopiclone and carbamazepine. 5. When the drugs were given together, the absorption of drugs was retarded. Carbamazepine-10,11-epoxide levels were lower after intake of the drug combination than those measured after intake of carbamazepine alone. 6. The results suggest that the clinical tests developed to detect alcohol effects do not necessarily reveal drug-induced impairment of performance.
Kuitunen
T
T
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Mattila
M J
MJ
Seppälä
T
T
Aranko
K
K
Mattila
M E
ME
D000328:Adult; D000435:Alcoholic Intoxication / Q000175:diagnosis; D053961:Azabicyclo Compounds; D002220:Carbamazepine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011597:Psychomotor Performance
D053961:Azabicyclo Compounds; D004338:Drug Combinations; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone; D002220:Carbamazepine