Reproductive toxicology profile of emtricitabine in mice and rabbits

Reproductive and developmental toxicology studies were conducted with emtricitabine, a nucleoside analog in development for treatment of human immunodeficiency virus (HIV) (Phase III) and hepatitis B (HBV) (Phase III) infections. Oral doses up to 1000 mg/kg/day provided daily area under the curve (AUC(0-->24)) exposure to pregnant animals approximately 60- (mice) to 120-fold (rabbits) higher than that in humans at the recommended dose of 200 mg given once per day. In a mouse fertility study, emtricitabine had no effect on fertility, sperm count, or early embryonic development. There was no increased incidence of malformations in mouse and rabbit embryofetal toxicology studies. The average ratio for concentration of emtricitabine in fetal plasma divided by concentration in maternal plasma was approximately 0.40 in mice and 0.50 in rabbits, a finding that indicates significant exposure of the fetuses to emtricitabine. The development and fertility of F(1) progeny were unaffected by emtricitabine in a mouse pre- and post-natal study. These data demonstrate a favorable pre-clinical reproductive safety profile for emtricitabine.