Abstract
Objective:
The main objective of this study was to investigate the pharmacokinetic characters
of eszopiclone (CAS: 138729-47-2) after single and multiple-dose oral administration
in healthy adult Chinese volunteers.
Methods:
In single-dose study, 12 subjects were given oral administrations of 1.5, 3 and 6 mg
eszopiclone in an open-label, randomized, crossover fashion. In multiple-dose study,
8 subjects were given 3 mg eszopiclone once daily consecutively for 7 days. Blood
samples were collected over 24 h and plasma eszopiclone were determined using a validated
liquid chromatography/mass spectrometry (LC/MS/MS) assay. The safety and tolerability
of eszopiclone was evaluated by adverse events recording, physical examination, laboratory
testing, vital signs, and 12-lead ECG findings.
Results:
The main pharmacokinetic parameters of eszopiclone after single-dose administration
were as follows: doses of 1.5, 3 and 6 mg; Cmax of 18.08±4.65, 38.29±15.41 and 76.38±23.34 ng/ml; Tmax of 0.94±0.39, 1.04±0.63 and 1.08±0.51 h; AUC0–24 of 110.90±23.06, 227.36±62.41 and 504.10±140.13 ng*h/ml; elimination half-lives of
5.84±1.03, 5.53±1.91 and 6.17±1.23 h. After multiple-dose administration, the steady-state
levels of eszopiclone were achieved by the 4th day, and the main pharmacokinetic parameters were Css_max at 33.43±5.63 ng/ml and AUCss (0–24) at 263.30±51.21 ng*h/ml. The most common adverse event was bitter or abnormal taste.
All the adverse events were judged as mild to moderate and resolved without any medication.
Conclusion:
The pharmacokinetic character of eszopiclone is linear and dose-proportional over
the range of 1.5–6 mg. The systemic exposure does not accumulate with once-daily administrations.
Eszopiclone appears to have good safety and is well tolerated.
Key words
eszopiclone - pharmacokinetics - safety - tolerability
