Driving under the influence of zopiclone: Elimination between two consecutive blood samples

Zopiclone is a widely used hypnotic drug which is frequently detected in apprehended drivers. For assessments in forensic cases, the elimination half-life (t_1/2) of a drug is sometimes important. A t_1/2 of 3.5-6.5 h for zopiclone is previously reported in healthy individuals, but different factors like age and drug-interactions can affect the t_1/2 of zopiclone. The aim of this study was to describe concentrations of zopiclone and co-ingestion of additional drugs in apprehended drivers, and to investigate the t_1/2 of zopiclone based on two consecutive blood samples.

Data was collected from apprehended drivers in Norway between 2003 and 2021. All cases where zopiclone was detected were included. In a subset of the material, two consecutive whole blood samples were collected ≥ 20 and < 60 min apart. Concentrations of zopiclone in blood were determined by LC-MS or UHPLC-MS/MS. The elimination and t_1/2 of zopiclone was estimated from the concentration change of zopiclone and the time interval between the two consecutive blood samples, under the assumption of first order kinetics.

The median concentration among all zopiclone positive cases was 0.044 mg/L (IQR 0.070 mg/L) (n = 2401). The most frequent additional drugs detected were ethanol (36%), diazepam (22%), amphetamine (14%) and THC (14%). In zopiclone-only cases (n = 364), the median concentration of zopiclone was 0.066 mg/L (IQR 0.115 mg/L). In 112 cases, two consecutive blood samples were collected. Of these, 28 cases showed increasing concentrations of zopiclone between the two sampling time points. Among the cases in which the concentration decreased (n = 84), the median C1 was 0.048 mg/L (IQR 0.062 mg/L) and the median C2 was 0.043 mg/L (IQR 0.056 mg/L). A Bayesian statistical model was used to obtain the posterior distribution of t_1/2. The posterior median of t_1/2 was estimated to 3.1 h (IQR=0.39 h) when including only the cases showing decreasing concentrations, and this increased to 3.8 h (IQR=0.52 h) when also including samples showing non outlying increase in concentrations. There was no statistically significant gender difference in the calculated half-lives (two-sided Mann-Whitney U test, p = .525).

This study showed that zopiclone is frequently detected in apprehended drivers in supra therapeutic concentrations and poly drug cases. The elimination of zopiclone in blood from two consecutive blood samples indicated an apparent t_1/2 of between 3.1 and 3.8 h, which is within the lower range of what previous experimental studies on healthy individuals have reported.