GV-196771A

Mice^[1]
Male wild-type FVB mdr1a/1b^+/+ and Pgp-deficient knockout FVBmdr1a/1b^-/- mice (20-30 g) are used. Dose solutions of 0.2 mg/mL for GV196771 and 5.0 mg/mL for GF120918 are prepared fresh using 0.5% hydroxypropylmethylcellulose and 1% Tween 80 as a vehicle. Two hours before the administration of GV196771, the animals are divided into two groups. One group receive a single oral dose (10 mL/kg) of vehicle and the second group receive a single 50 mg/kg oral dose (10 mL/kg) of GF120918. Two hours later, all animals receive a single 2 mg/kg oral dose (10 mL/kg) of GV196771. At scheduled time points, mice are anesthetized with CO₂ and blood samples are obtained by cardiac puncture. Blood is centrifuged to yield plasma. The MDR genotype of each animal is confirmed by a polymerase chain reaction assay after study completion.

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