Effects of co-administration with morin and acetyl-resveratrolon pharmacokinetics of saquinavir in rats / 中国药理学通报

ABSTRACT

Aim To assess the impact of morin and acetyl-resveratrol on the oral bioavailability and pharmacokinetics of saquinavir (SQV), a substrate of P-glycoprotein (P-gp), in rats.Methods Twenty rats were randomized into four groups of equal size, including a control group, two intervention groups and a positive control group, and administered orally 30 mg·kg-1 SQV with or without 40 mg·kg-1 morin or acetyl-resveratrol or verapamil (as positive control).The plasma concentrations of saquinavir were determined using a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and the PK of SQV was assessed using non-compartmental analysis.Results The PK parameters values of SQV, SQV+morin, SQV+acetyl-resveratrol, SQV+verapamil were as follows AUC0-t, 381.53 μg·h·L-1,185.53 μg·h·L-1, 360.43 μg·h·L-1, 529.95 μg·h·L-1;AUC0-∞, 409.48 μg·h·L-1, 228.52 μg·h·L-1,446.67 μg·h·L-1, 552.41 μg·h·L-1;Cmax, 110.80 μg·L-1, 86.44 μg·L-1, 139.84 μg·L-1, 423.60 μg·L-1;Tmax, 0.25 h, 0.25 h, 0.25 h, 0.50 h;T1/2, 5.72 h, 5.94 h, 6.78 h, 3.78 h;MRT0-∞, 10.30 h, 9.61 h, 12.30 h, 4.89 h;CL/F, 7.59 mL·kg-1·h-1, 13.88 mL·kg-1·h-1, 7.28 mL·kg-1·h-1, 5.52 mL·kg-1·h-1.Conclusions Multiple peak phenomenon can be observed in the plasma SQV profiles.Morin can significantly reduce the SQV oral bioavailability and affect SQV PK profiles while acetyl-resveratrol cannot significantly affect the SQV oral bioavailability and SQV PK profiles in rats.