Pharmacokinetics Study Of Eszopiclone

Objective:To perform Phase I pharmacokinetics study of eszopiclone. Includes:1. Single dose pharmacokinetics research. To demonstrate the PK profile of eszopiclone in health subject after a single dose has been received. Three doses level were taken, and information about the PK characterization, type of compartment model, as well as linear dynamics were obtained.2. Effect of food on absorbing of eszopiclone. To compare the PK profile of eszopiclone administered before and after eating.Method : 1 . Establishment of analytical method of plasma concentration of eszopiclone.Prepared a standard curve of blood sample of eszopiclone, and validated by methodology.2.Pharmacokinetics and the influence of food on metabolism of drug were evaluated.After received the test medicine, blood drug levels were determined by HPLC and main parameters of AUC,Cmax etc. were calculated.Results:The elimination half-life of 3mg, 6mg and 12mg eszopiclone group are 6.98±0.99, 8.20±6.14 and 8.06±2.82hr, respectively. AUC0-t are 238.84±78.97, 377.17±70.49 and 1209.17±399.13μg/hr/L, respectively. Clearance (CLs) are 14.1±4.5, 15.8±3.0 and 10.9±5.0L/hr, respectively. Tmax are 1.5±0.66, 1.28±0.43 and 1.58±0.40hr. Cmax are 33.96±8.63, 60.94±11.44 and 182.72±67.44μg/L;the Vd value of 6mg and 12mg eszopiclone group are 79.0±16.9 and 65.4±17.2L, respectively.To compare the oral eszopiclone PK profile on fasting and eating status, show that food have some effect on metabolism and clearance of eszopiclone. These influence include: reduced AUC0-t and enhanced clearance.Conclusion:Eszopiclone oral tablet absorb rapidly. Within the range of 3-12mg, dose have linear relationship with blood drug level. Absorption and distribution of eszopliclone is close to zopiclone, but a little higher Cmax, t1/2 and AUC value, which suggest that eszopiclone may have a lower effective dosage than zopiclone. Common but minor ADR of eszopiclone is bitter taste and dizziness, support that the medicine have well safety profile.