Pharmacokinetic Studies in Rat

Specific pathogen-free (SPF) grade male Sprague–Dawley (SD) rats (weight: 230±10 g) were provided by the Laboratory Animal Resources Institute of the National Institutes for Food and Drug Control (Beijing, China). The license number is SCXK (Beijing) 2017–0005. The animal experiment protocols were approved by the Experimental Animal Welfare Ethics Committee of Hebei Medical University (Shijiazhuang, China) and were conducted in accordance with the Guide for the Care and Use of Laboratory Animals. Rats were fed twice a day in an appropriate environment at 18–24 °C and 40–60% humidity. Before the experiment, the rats were fasted overnight without lack of water. A total of 12 rats were randomly and equally divided into two groups: experimental and control. The two groups were administered 72 mg/kg ESL and the corresponding volume of solvent (0.5% sodium carboxymethyl cellulose) intragastrically for 7 consecutive days, respectively. On day 7, rats in both groups were given 1 mg/kg PER by intragastric administration 30 min after administration of ESL or solvent. At 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, and 24 h after the last administration, a volume of 150 µL blood sample was collected from venous plexus of the inner canthus into heparinized tubes. The supernatant obtained by centrifugation at 3000 rpm for 10 min was stored at −20 °C until analysis.