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The pharmacokinetic study was performed using a parallel design. A total of 18 Sprague-Dawley rats (weight of 240 ± 10 g) were randomly assigned to three groups, with each group having six rats. The rats were subjected to overnight fasting for 12 h and were administered the optimized SSM SNEDDS formulation or SSM suspension orally (100 mg/kg, p.o.). The orally administered SSM suspension was composed of SSM and 2% CMC solution (w/v). For repetitive blood sampling, we applied a jugular vein catheterization model [37]. The rats were anesthetized, and polyethylene tubes were implanted into the right jugular veins. Blood samples (300 μL) were collected in heparinized tubes before dosing (0 min); at 5, 15, and 30 min after dosing; and at 1, 2, 4, 6, 8, 10, 12, and 24 h after dosing. For the IV bolus administration group, each rat was administered the SSM solution formulation (1 mg/kg) through the femoral vein; the IV solution comprised DMSO/PEG 400 (50:50, v/v). Blood samples were collected as blanks before IV administration; at 1, 5, 10, 20, and 40 min after IV administration; and at 1, 2, 4, 6, and 8 h after IV administration. An equal volume of heparinized normal saline replaced the blood removed at each sampling point. Each sample was centrifuged at 3000× g for 10 min, and the plasma supernatant was separated and stored at −70 °C for analysis within 24 h.

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