QUANTITATIVE ASSESSMENT AND TIME KINETICS OF ZOPICLONE (THE MOST USED HYPNOTIC DRUG) IN THE STORED BLOOD SAMPLES

Ismail Khalil*, Mohammed Jasim and Ali Kadhim

ABSTRACT

Background: Zopiclone is a hypnotic short-acting agent used in the treatment of primary insomnia. After oral administration, zopiclone is rapidly absorbed and has a bioavailability of about 80%. Zopiclone is metabolized extensively in the liver, but the CYP isoforms involved in its metabolism have not yet been identified. Objective: To estimate the zopiclone levels in the drawn plasma of volunteers at different time points after storage under refrigeration. To collect data about the insomnia or sleepiness after 24hours of single oral dose of zopiclone. Methods: There were totally 42 volunteers belonging to the age groups 22-44 years, 45-60 years and 61-76 years group. Drug administration: The volunteers were given an oral dose of zopiclone (5mg) tablet and blood collected at various intervals as follows: 1- After administration, blood samples were collected at 0, 1, 2, 3, 4, 6, 12, 18, 24, 48h and plasma separated for zopiclone estimation. 2- After administration, after 2 hours the blood was collected and plasma separated, which was stored in refrigerator for analysis at various intervals to see the stability of the zopiclone. 3- Urinary levels of Zopiclone was also measured in all the groups. Results: In our study, we demonstrated that following the single administration of oral tablet of Zopiclone, the plasma levels diminish very slowly taking upto 48 hours. Some traces of Zopiclone were identifiable upto 72 hours (not presented here). The major difference was the relapse of insomnia very fast among the elderly population and middle aged groups in comparison to the younger group of 22-44 years. In addition, the storage of plasma even under refrigeration resulted in fast degradation of zopiclone in the samples. This suggests strongly that, the zopiclone should be estimated as the sample is fresh. In addition the zopiclone values from stored samples need verification with other assays. Conclusion: Z-drugs have few distinct advantages over their predecessors, the benzodiazepines, and in many ways they have similar adverse and toxic effects, especially zopiclone. The effects of Z-drugs largely derive from their GABA ergic action and pharmacokinetic profiles, which decide the extent of efficacy and toxicity. Adverse Z-drug effects and toxicity are more likely with poly drug use in therapeutics and co-ingested psychoactive substances in overdose.

Keywords: Insomnia, Zopiclone.