Zopiclone pharmacokinetics

Of the non-benzodiazepines that have been introduced recently for the treatment of anxiety and insomnia, buspirone and zopiclone have been the most extensively investigated so far. The pharmacokinetic characteristics of... 

Drover DR Comparative pharmacokinetics and pharmacodynamics of short-acting hypnosedatives Zaleplon, zolpidem and zopiclone. Clin Pharmacokinet 2004 43 227. [PMID 15005637]... 

The newer sedative-hypnotics that are not benzodiazepines are rapidly becoming the first-line treatment for insomnia. These agents not only have pharmacodynamic advantages over benzodiazepines in terms of their mechanism of action, but perhaps more importantly, pharmacokinetic advantages as well. Three nonbenzodiazepine sedative-hypnotic agents that are now available are zaleplon (a pyrazolopyrimidine), zopiclone (a cyclopyrrolone not available in the United States), and zolpidem (an imidazopyridine) (Figs. 8—28-8—30 Table 8—4). 

Gaillot J, Le Roux Y, Houghton GW, Dreyfus JF (1987) Critical factors for pharmacokinetics of zopiclone in the elderly and in patients with liver and renal insufficiency. Sleep 10 7-21... 

Gaillot J, Heusse D, Houghton D, Aurele JM, Dreyfus J (1983) Pharmacokinetics and metabolism of zopiclone. Pharmacology 27 (Suppl 2) 76-91... 

Fernandez C, Martin C, Gimenez F, Farinotti R (1995) Clinical pharmacokinetics of zopiclone. Clin Pharmacokinet 29 431-441... 

As far as is currently known, benzodiazepines and similar drugs (zopiclone, zolpidem) act by a single mechanism, interacting at the GABA receptor complex to enhance the ability of GABA to open a chloride ion channel and thereby hyperpolarize the neuronal membrane. It is usual, therefore, to classify benzodiazepines, and recommend their clinical use, on the basis of their duration of action or their half-life. While this is without doubt a useful classification, it is simplistic and does not take into account other important pharmacokinetic factors. 

The addition of alcohol to the Z drugs, zaleplon, Zolpidem, and zopiclone, produces additive sedative effects without altering their pharmacokinetics (20). 

Goa KL, Heel RC. Zopiclone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy as an hypnotic. Drugs 1986 32(l) 48-65. 

To date, no clinically significant pharmacokinetic interactions between alcohol and zopiclone have been reported. Zolpidem enhances alcohol performance impairment (the effect appears to be short-lived). ... 

Fernandez, C. Maradeix, V. Gimenez, F. Thuillier, A. Farinotti, R. Pharmacokinetics of zopiclone and its enantiomers in Caucasian young healthy volunteers. Drug Metab. Dispos. 1993, 21, 1125-1128. 

Several studies have reported that alcohol increases plasma levels of diazepam and that alcohol accelerates the absorption of diazepam, but others have suggested that alcohol has no significant effect on diazepam pharmacokinetics. Plasma levels of brotizolam and clobazam may be increased by alcohol. One study reported that the plasma levels of triazolam were increased by alcohol, but other studies have found only a minimal pharmacokinetic interaction. However, an in vitro study demonstrated that alcohol inhibited the metabolism of triazolam by the cytochrome P450 isoenzyme CYP3A. Another in vitro study reported that the formation of flunitrazepam metabolites was weakly inhibited by alcohol, but a pharmacokinetic study suggested that there was no interaction. Alcohol appears to have minimal effects on the pharmacokinetics of alprazolam, and zopiclone. ... 

The pharmacokinetics of alcohol do not appear to be affected to a clinically significant extent by diazepam, flunitrazepam, zolpidem, or zopiclone but alprazolam may increase blood-alcohol levels. 

Zaleplon, zolpidem and zopiclone are metabolised by several cytochrome CYP450 isoenzymes and it has been suggested that because of this, other drugs which affect a particular isoenzyme such as CYP3A4, may have less effect on their metabolism. However, their pharmacokinetics are affected by potent inducers such as rifampicin and by inhibitors such as the azole antifungals. Buspirone undergoes CYP3A4-mediated metabolism in the liver. 

Jalava K-M, Olkkola KT, Neuvonen PJ. Effect of itraconazole on tiie pharmacokinetics and pharmacod3mamics of zopiclone. EurJ ClinPharmacol (1996) 51, 331-4. 

Aranko K, Luurila H, Backman JT, Neuvonen PJ, Olkkola KT. The effect of erytiiromycin on the pharmacokinetics and pharmacod3mamics of zopiclone. BrJ Clin Pharmacol (1994)... 

Zopiclone appears to counter the stimulant effects of caffeine more easily than caffeine counters the sedative effects ofzopiclone. No pharmacokinetic interaction occurred between zolpidem and caffeine (given as one cup of coffee containing caffeine 300 mg), and the hypnotic effects of zolpidem were unchanged. ... 

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