2.12. Pharmacokinetic study of paclitaxel

Rats were randomly divided into six groups (6/group) receiving 50 mg/kg of type I POPs orally and 6 mg/kg of paclitaxel intravenously. Vehicle B (ethanol/Tween 80/saline, 5%/5%/90% was used to prepare paclitaxel solution. Dosage regimen and sampling procedures were: group 1 or 2, vehicle A or type I POPs was administered 8 h prior to paclitaxel; group 3 or 4, vehicle A or type I POPs was administered once-daily for 7 consecutive days. On Day 7, paclitaxel was given at 8 h after type I POPs. For groups 1–4, blood (0.2 mL/sample) was collected as aforementioned with saline compensation at 0, 2, 5, 15, and 30 min, and 1, 2, 4, 6, 8, 10, 12, and 24 h, and feces and urine were collected within 0–24 h after paclitaxel dosing; group 5 or 6, vehicle A or type I POPs was given 8 h prior to paclitaxel once-daily for 6 consecutive days. On Day 1, five blood samples were collected at 5 min prior to type I POPs dosing, 5 min prior to paclitaxel dosing, and 2 min, 1 h, and 8 h after paclitaxel dosing. During Days 2–6, three blood samples were collected at 5 min prior to type I POPs dosing, 5 min prior to paclitaxel dosing and 2 min after paclitaxel dosing. On Day 6, pharmacokinetics of paclitaxel was monitored by measuring blood samples collected at 2, 15, and 30 min, and 1, 3, 6, 8, and 24 h after its last-dose. Tissue (heart, liver, spleen, lung, kidney, and brain) specimens were collected at the end of experiments. The collected blood samples were centrifuged at 6000×g for 10 min to obtain plasma, feces, and urine samples were weighed, and tissue specimens were washed with cold PBS, blotted dry, and weighed. All these samples were stored at −80 °C until LC–MS analysis.