Embryo-Fetal Developmental Toxicity and Toxicokinetics Studies of YWS1903, a Novel Potassium-Competitive Acid Blocker, in Pregnant Rats

The study investigated the developmental and reproductive toxicity of YWS1903, a novel potassium-competitive acid blocker, in pregnant Sprague–Dawley rats. YWS1903 was administered at doses of 0, 20, 60, and 200 mg/kg to 24 rats per group. Hair loss was observed at the highest dose, but no significant maternal toxicity was noted up to 200 mg/kg. Fetal assessments at 200 mg/kg showed reduced body weight and crown-rump length, and increased skeletal malformations, but no visceral abnormalities. Toxicokinetic analysis indicated potential saturation of metabolic pathways at higher doses, with YWS1903 crossing the placenta but resulting in lower fetal plasma concentrations. The no observed adverse effect level was 60 mg/kg, suggesting safety at moderate doses and providing insights for its clinical use in treating gastroesophageal reflux disease.