Comparison of developmental toxicity of selective and non-selective cyclooxygenase-2 inhibitors in CRL:(WI)WUBR wistar rats : DFU and piroxicam study

摘要: Abstract Background: Cyclooxygenase (COX) inhibitors are one of the most often ingested drugs during pregnancy. Unlike general toxicity data, their prenatal toxic effects were not extensively studied before. The aim experiment was to evaluate developmental non-selective (piroxicam) and selective (DFU; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon) COX-2 inhibitors. Methods: Drugs separately, orally once daily dosed pregnant rats from day 8 21 (GD1 = plug day). Doses set at 0.3, 3.0 30.0 mg/kg for piroxicam 0.2, 2.0 20.0 mg/kg DFU. Fetuses delivered on GD routinely examined. Comprehensive clinical measurements done. pooled statistical analysis ventricular septal (VSD) midline (MD) defects performed rat fetuses exposed piroxicam, inhibitor based present historic data. Results: Maternal toxicity, intrauterine growth retardation, increase external skeletal variations found in treated with highest dose piroxicam. Decrease fetal length only signs DFU observed pups compound dose. Lack teratogenicity DFU-exposed groups. Prenatal exposure COX increases risk VSD MD when compared control but Conclusion: Both administered DFU, also highly dams. does control.