GV-196771A

Animal experiment:

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.

References:

[1]. Polli JW, et al. The systemic exposure of an N-methyl-D-aspartate receptor antagonist is limited in mice by the P-glycoprotein and breast cancer resistance protein efflux transporters. Drug Metab Dispos. 2004 Jul;32(7):722-6.