Morphological and Skeletal Abnormalities Induced by Rolapitant: An Antiemetic Agent

Abstract

IntroductionRolapitant hydrochloride is a highly selective, long-acting antagonist of the neurokinin-1 (NK1RA) receptor with a high level of central nervous system (CNS) penetrance. Clinically, it is given to cancer patients with high and moderate emetogenic chemotherapy to prevent chemotherapy-induced nausea and vomiting (CINV). The facts produced in this research support the interpretation of teratogenic effects like anatomical malformations and abnormal skeletal changes affected by high doses of rolapitant in developed chick embryos, which can be extrapolated to humans due to gaps in the literature regarding the teratogenic potential of rolapitant. As rolapitant is metabolized by the liver and excreted through the kidney by leaving a deep impact on the various systems of the body and due to its high plasma concentration with a half-life of more than 180 hours, the study was conducted to acquire some additional information about its adverse effects over the various body systems. Chick is one of the best animals for embryological laboratory research. For various reasons, it is preferred to research embryology in chicks or domestic hens (Gallus domesticus). Chick eggs are large, readily available all year, easy to incubate, and regulate artificially.AimThis study aimed to determine the morphological and skeletal abnormalities due to the effect of rolapitant, an antiemetic agent, in developing White Leghorn (G. domesticus) chicken eggs.Materials and methodsThe experiment used 300 fertilized White Leghorn chicken eggs. The eggs were categorized into five experimental groups (A, B, C, D, and E, each with 30 eggs) and five control groups (a, b, c, d, and e, each with 30 eggs). Rolapitant was administered into the five experimental groups of eggs on incubation day five at various concentrations of 0.00039, 0.0005, 0.00075, 0.001, and 0.00125 mg, respectively, while the control groups received the same volume (0.039, 0.05, 0.075, 0.1, and 0.125 ml, respectively) of normal saline.ResultsAt all doses, the mean weight and crown-rump (CR) length of chick embryos were significantly greater in the control group than in the experimental group. The experimental group died at a higher rate than the control group. Additionally, it was found that the mortality due to the rolapitant dosages increases with dose. All groups except group A showed skeletal anomalies such as poor ossification, bent, and displacement, and morphological abnormalities such as yolk sac retraction, hematoma, and scanty feathers were found in experimental groups C, D, and E. This was shown to be more prevalent in the experimental groups and was exacerbated by subsequent rolapitant dosages.ConclusionRolapitant is toxic when taken in large doses and for an extended period. As a result, rolapitant should be taken only when a valid diagnosis has been established and only at the recommended dose, not at a larger dose or for an extended period of time.