Evaluation of Teratogenic Profile of Combination of Lumacaftor and Ivacaftor in Sprague–Dawley Rats

ABSTRACT

Background: 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. Results: In pregnant rats exposed to Lumacaftor and Ivacaftor, the external examination was conducted on 206, 209, 199, 184, 198 and 201 foetuses in their respective groups, each consisting of 19 litters. Within this cohort, approximately 33% of foetuses underwent visceral examination. Additionally, across six groups approximately 50% of foetuses underwent skeletal examination. Importantly, no abnormalities were detected in skeletal, visceral or histopathological assessments across the treatment groups encompassing doses of a combination of Lumacaftor and Ivacaftor at MRHD, 5MRHD, 8MRHD and 10MRHD. Additionally, no significant morbidity or mortality related to the treatment was observed. Conclusion: In conclusion, the study indicates that the combination of Lumacaftor and Ivacaftor at doses equivalent to MRHD, 5MRHD, 8MRHD and 10MRHD did not induce significant teratogenic effects, affirming their safety during pregnancy in rats.

KEYWORDS

• Lumacaftor/Ivacaftor
• teratogenicity
• skeletal examination
• external malformations
• alizarin red S

Showing references and in-text citations exactly as published.

Cite this article

• DOI10.1177/0976500X241240631Copy

RELATED ARTICLES

Matched on section and article type within this issue of J Pharmacol. Pharmacother..

• Article · VOLUME 15, ISSUE 2Perioperative Cardiopulmonary Complications in Smokers and Non-smokers Undergoing Elective Surgery: A Prospective StudyVenumula Vikram Reddy, Dinakar Mallem, Sonnaila Rama Krishna, Vijay Kotra, Wen Han Chooi, Khang Wen Goh, Long Chiau Ming, Mahibub Mahamadsa Kanakal, Syed Atif Abbas, Khairulanwar Husain · pp. 171–182Research ArticleSame type: Article
• Article · VOLUME 15, ISSUE 2Evaluation of Pharmacotherapy of Cancer Pain in Patients with Head and Neck Cancer at a Tertiary Care Teaching HospitalShyam Vacchani, Megha Shah, Chetna Desai, Priti Sanghvi · pp. 183–189Research ArticleSame type: Article
• Article · VOLUME 15, ISSUE 2Influence of Ascorbic Acid on Di-(2-Ethylhexyl) Phthalate-induced Ovarian Gene Alterations in Pubertal Female Wistar RatsShifana Ali, Ahmed Ziyad, Karkala Sreedhara Ranganath Pai, Anju Muraleedharan, Adhithya Gopan, Raghavendra Upadhya, Raviraja N Seetharam, Kalaivani Manokaran · pp. 190–199Research ArticleSame type: Article
• Article · VOLUME 15, ISSUE 2Embodiment of Pharmacist Intervention in Palliative Care and Augmentation of a Curriculum for its AssessmentAnn Lithia Thomas, Asiya Nasouha, Aswanth Anil, Dilip Chandrasekhar, Pallavi Palasseri · pp. 200–206Research ArticleSame type: Article