Effect of Paxlovid on Skeletal System Morphogenesis in Animal Model Rat (Morphological Study).

Background: Paxlovid, an investigational oral therapeutic comprising Nirmatrelvir (NMV) and Ritonavir, is being developed to treat SARS-CoV-2 infections and reduce the risk of severe disease, hospitalization, and mortality. This study evaluates the effects of Paxlovid on the skeletal morphogenesis of rat fetuses at doses up to 1000 mg/kg/day, adhering to the International Council for Harmonisation guidelines for embryo-fetal development studies. Methods: In this morphological study of the morphogenesis of the skeletal system, Pregnant rats were allocated into four groups (one control and three subjected to varying treatment levels). fetal weight, crown-rump length (CRL), and abdominal circumference (AC) were measured. Skeletal abnormalities were assessed using double staining with Alizarin red S and Alcian blue. Data were evaluated using Microsoft Excel. One-way analysis of variance (ANOVA) was performed to compare fetal weight, CRL, and AC among the experimental groups and the control group. When significant differences were detected, Tukey's Honestly Significant Difference (HSD) test was used for post hoc comparisons. Statistical analysis was conducted using XLSTAT 2016 software, and a p-value of < 0.05 was considered statistically significant. Results: Results indicated that mothers in the Paxlovid treatment groups experienced less weight gain compared to controls (252 ± 19.84 g, 224.1 ± 14.1 g, 232.1 ± 15.5 g, 246.2 ± 12.8 g, respectively, on GD21). On GD (gestational day) 21, fetuses from treatment groups exhibited reduced weight (3.5 ± 0.6 g, 1.7 ± 0.8 g, 1.8 ± 0.8 g, 2.5 ± 0.3 g, respectively), CRL (35 ± 3.8 mm, 25.9 ± 6.5 mm, 26.36 ± 6.2 mm, 31.58 ± 2.2 mm, respectively), and AC (12.2± 1.2 mm, 9.9 ± 1.4 mm, 9.8 ± 1.6 mm, 11 ± 1 mm, respectively) compared to controls; however, no skeletal abnormalities were detected through staining methods. Conclusion: The findings suggest that while there are observable effects on maternal weight and fetal growth parameters, the administration of Paxlovid did not result in skeletal system abnormalities in the embryos. This research indicates a minimal risk of fetal harm associated with Paxlovid use, reinforcing its safety profile regarding fetal development. These results contribute to the understanding of Paxlovid's implications for pregnant individuals and support its potential therapeutic use against SARS-CoV-2.