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Updated: Jun 23, 2026
Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C)
Published on: March 25, 2016
Preliminary embryo-fetal developmental toxicity study of pritelivir in CD1-IGS mice
Tatiana N Nanovskaya1, Svetlana L Patrikeeva1, Xiaoming Wang1
1Maternal-Fetal Pharmacology and Bio-Development Laboratories, Department of Obstetrics & Gynecology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0587, USA.
Abstract:
Pritelivir is a novel anti-herpes simplex virus drug that is currently in clinical trials in nonpregnant immunocompromised subjects. Here we conducted a preliminary embryo-fetal developmental toxicity study of pritelivir in CD1-IGS mice. Pritelivir was administered by oral gavage to time-mated mice at dose levels of 0, 10, 60 and 200 mg/kg/day from gestational day 6 through 15. Maternal food consumption, body weight and clinical observations were monitored throughout gestation. The mice were sacrificed at gestational day 18 and assessed based on embryo-fetal development and viability. Fetuses were weighed and examined for external and visceral variations and malformations. The results showed that exposure to pritelivir did not cause maternal or developmental toxicity in mice. Thus, both maternal and fetal no-observed-adverse-effect-level of pritelivir was determined to be 200 mg/kg/day. At this dose, the area under the concentration-time curve for pritelivir at steady state in maternal animals was 20 times greater than reported in humans at the clinical dose of 100 mg/day. Placenta-to-maternal plasma and fetus-to-maternal plasma concentration ratios in mice were 0.4 and 0.2, respectively, indicating transfer but not accumulation of pritelivir in the fetoplacental compartment. Taken together, our findings support further preclinical studies of pritelivir for its use in pregnancy.
Insights
Pritelivir, an anti-herpes simplex virus drug, showed no maternal or developmental toxicity in a preliminary mouse study. The no-observed-adverse-effect level was 200 mg/kg/day, supporting further research for use in pregnancy.
Area of Science:
- Pharmacology
- Toxicology
- Reproductive Science
Background:
- Pritelivir is a novel antiviral agent targeting herpes simplex virus.
- Current clinical trials exclude pregnant individuals.
- Understanding embryo-fetal toxicity is crucial for potential use in pregnancy.
Purpose of the Study:
- To assess the embryo-fetal developmental toxicity of pritelivir in CD1-IGS mice.
- To determine the maternal and fetal no-observed-adverse-effect level (NOAEL) of pritelivir.
- To evaluate pritelivir transfer into the fetoplacental compartment.
Main Methods:
- Oral gavage administration of pritelivir (0, 10, 60, 200 mg/kg/day) to time-mated mice from gestational day 6-15.
- Monitoring of maternal parameters including food consumption and body weight.
- Post-sacrifice examination of fetuses for viability, weight, external, visceral variations, and malformations.
Main Results:
- Pritelivir exposure did not induce maternal toxicity or developmental abnormalities in mice.
- The maternal and fetal NOAEL for pritelivir was established at 200 mg/kg/day.
- Placental and fetal exposure levels indicated transfer without accumulation, with ratios of 0.4 and 0.2 respectively.
Conclusions:
- Pritelivir demonstrates a favorable safety profile in a preliminary embryo-fetal developmental toxicity study in mice.
- The determined NOAEL in mice suggests a wide safety margin compared to human clinical doses.
- Findings support continued preclinical investigation of pritelivir for potential use during pregnancy.
