The individual teratogenicity profiles of Lumacaftor and Ivacaftor are known, but the combined effects remain unexplored.
Purpose
To evaluate the teratogenic profile of a combination of Lumacaftor and Ivacaftor in Sprague-Dawley Rats.
Materials and Methods
This study adhered to the Committee for Control and Supervision of Experiments on Animals (CCSEA) and Organisation for Economic Co-operation and Development (OECD) guidelines. Sprague–Dawley rats were acclimated and housed individually under controlled conditions. A polygamous breeding scheme was implemented, and pregnant female rats were assigned to control, vehicle control or treatment group following OECD Test Guideline 414. Lumacaftor and Ivacaftor were administered to pregnant rats at various doses, such as MRHD, 5MRHD, 8MRHD and 10MRHD, from gestation days 6 to 17. Clinical observations, body weight and food consumption of pregnant rats were monitored. Postmortem examinations included caesarean section, reproductive performance (the number of corpora lutea, implantation sites, early and late resorptions and live foetuses) and assessment of foetal analysis. The foetal analysis incorporated external malformation evaluation, visceral examination and skeletal examination using alizarin red solution.