Pharmacokinetic and clinical parameters of zopiclone and trimipramine when administered simultaneously to volunteers

Caillé, Gilles; Souich, Patrick du; Spénard, Jean; Lacasse, Yves; Vézina, M.

doi:10.1002/bdd.2510050205

Cited by 30 publications

(15 citation statements)

References 10 publications

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“…However, zopiclone pharmacokinetics without concomitant alcohol were not investigated, pre- venting a conclusion as to the effect of ethanol on zopiclone pharmacokinetics. In healthy individuals, coadministration of zopiclone and trimipramine resulted in decreased bioavailability of both drugs, by 13.7% and 26.6% respectively, compared with single-agent administration) 19 1 However, these reductions did not have statistical significance. Other pharmacokinetic parameters were not modified.…”

Section: Drug Interactionsmentioning

confidence: 95%

Clinical Pharmacokinetics of Zopiclone

Fernandez

Martin

Gimenez

et al. 1995

Clinical Pharmacokinetics

223

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Zopiclone is a cyclopyrrolone hypnotic agent. It possesses a chiral centre and is commercially available as a racemic mixture. Methods involving high performance liquid chromatography (HPLC), gas chromatography, capillary electrophoresis (CE) and high performance thin layer chromatography have been developed for the quantitation of zopiclone and its 2 main metabolites in biological samples. For the chiral determination of the enantiomers of zopiclone and its metabolites, HPLC and CE methods are available. After oral administration, zopiclone is rapidly absorbed, with a bioavailability of approximately 80%. The plasma protein binding of zopiclone has been reported to be between 45 and 80%. Zopiclone is rapidly and widely distributed to body tissues including the brain, and is excreted in urine, saliva and breast milk. Zopiclone is partly metabolised in the liver to form an inactive N-demethylated derivative and an active N-oxide metabolite. In addition, approximately 50% of the administered dose is decarboxylated and excreted via the lungs. Less than 7% of the administered dose is renally excreted as unchanged zopiclone. In urine, the N-demethyl and N-oxide metabolites account for 30% of the initial dose. The terminal elimination half-life (t1/2z) of zopiclone ranges from 3.5 to 6.5 hours. The pharmacokinetics of zopiclone in humans are stereoselective. After oral administration of the racemic mixture, Cmax (time to maximum plasma concentration), AUC (area under the plasma time-concentration curve) and t1/2z values are higher for the dextrorotatory enantiomer owing to the slower total clearance and smaller volume of distribution (corrected by the bioavailability), compared with the levorotatory enantiomer. In urine, the concentrations of the dextrorotatory enantiomers of the N-demethyl and N-oxide metabolites are higher than those of the respective antipodes. The pharmacokinetics of zopiclone are altered by aging and are influenced by renal and hepatic functions. Drug interactions have been observed with erythromycin, trimipramine and carbamazepine.

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Section: Drug Interactionsmentioning

confidence: 95%

Clinical Pharmacokinetics of Zopiclone

Fernandez

Martin

Gimenez

et al. 1995

Clinical Pharmacokinetics

223

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“…In a study of zopiclone, the mean concentration in oral fluid 24 h after oral administration of 7.5 mg was 2 ng/ml (10). Therefore, the prevalence of use of 7.5 mg during the last 24 h can be estimated by using a cutoff of 2 ng/ml.…”

Section: Zopiclonementioning

confidence: 99%

Can the use of psychoactive drugs in the general adult population be estimated based on data from a roadside survey of drugs and driving?

Gjerde

Normann²,

Mørland³

2011

Nor J Epidemiol

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A roadside survey of drugs and driving was performed in south-eastern Norway in 2005-6. Samples of saliva from a total of 10,503 drivers above 20 years of age were analysed, and the results were weighted for under-and over-sampling compared to the population distribution in the study area. Weighted results were compared with data on dispensed prescriptions of zopiclone, codeine and diazepam at Norwegian pharmacies in the same area and with self-reported use of cannabis. When using roadside data to estimate drug use, the use of medicinal drugs was under-estimated by 17-59% compared to amounts dispensed. One of the main reasons for the under-estimation may be that a large proportion of the users of psychoactive medicinal drugs are not frequent drivers. For cannabis, self-reported data corresponded approximately to the estimated prevalence range. The results indicate that roadside surveys cannot be used for accurate estimations of drug use in the population, but may provide minimum figures.

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“…Only a few studies describe trimipramine kinetics in man (3)(4)(5) and results show differences especially in determination of the half-life.…”

Section: Introductionmentioning

confidence: 99%

Chronopharmacokinetic and bioequivalence studies of two formulations of trimipramine after oral administration in man

Bougerolle

Chabard

Jbilou

et al. 1989

Eur. J. Drug Metab. Pharmacokinet.

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The bioavailability of two oral formulations of trimipramine, tablets and solution, was performed in twelve healthy volunteers, in a cross-over study. Each formulation was administered in the morning after a fasted period, and in the evening after a meal, in order to evaluate the role of both administration time and food consumption on the plasma kinetic parameters, under usual therapeutic conditions. A high interindividual variability of data was found. First, the extent of bioavailability was identical for the two formulations but the rate of bioavailability seemed to be different, with the p.o. solution, being more rapidly absorbed (tmax = 1.50 h). The effect of administration time was more obvious for the solution as shown by a lower quantitative absorption as well as a delay in time to reach the maximal concentration. Regardless of formulation and administration time, the t1/2 beta was about 10 hours and the mean MRT value was 11 hours.

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Pharmacokinetic and clinical parameters of zopiclone and trimipramine when administered simultaneously to volunteers

Cited by 30 publications

References 10 publications

Clinical Pharmacokinetics of Zopiclone

Clinical Pharmacokinetics of Zopiclone

Can the use of psychoactive drugs in the general adult population be estimated based on data from a roadside survey of drugs and driving?

Chronopharmacokinetic and bioequivalence studies of two formulations of trimipramine after oral administration in man

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