Considerations for and against dosing rodent pups before 7 days of age in juvenile toxicology studies

Schmitt, Georg; Barrow, Paul

doi:10.1016/j.reprotox.2022.06.010

Cited by 2 publications

(1 citation statement)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, we examined morphine and U50, 488 thermal antinociception and oral fentanyl self-administration in both male and female rats. The fentanyl exposure time frame was chosen as it is roughly analogous to the last trimester of human pregnancy in terms of brain development ( Schmitt and Barrow, 2022 ). While the third trimester only is not the most common exposure period for human women, it does represent a significant percentage of women who are prescribed opioids for pain during pregnancy ( Cook, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of neonatal fentanyl on late adolescent opioid-mediated behavior

Crawford

Taylor²,

Park³

et al. 2023

Front. Neurosci.

View full text Add to dashboard Cite

IntroductionBecause of the steady increase in the use of synthetic opioids in women of childbearing age, a large number of children are at risk of exposure to these drugs prenatally or postnatally through breast milk. While there is older literature looking at the effects of morphine and heroin, there are relatively few studies looking at the long-term effects of high-potency synthetic opioid compounds like fentanyl. Thus, in the present study, we assessed whether brief exposure to fentanyl in male and female rat pups during a period roughly equivalent to the third trimester of CNS development altered adolescent oral fentanyl self-administration and opioid-mediated thermal antinociception.MethodsWe treated the rats with fentanyl (0, 10, or 100 μg/kg sc) from postnatal day (PD) 4 to PD 9. The fentanyl was administered daily in two injections given 6 h apart. After the last injection on PD 9, the rat pups were left alone until either PD 40 where they began fentanyl self-administration training or PD 60 where they were tested for morphine- (0, 1.25, 2.5, 5, or 10 mg/kg) or U50,488- (0, 2.5, 5, 10, or 20 mg/kg) induced thermal antinociception.ResultsIn the self-administration study, we found that female rats had more active nose pokes than male rats when receiving a fentanyl reward but not sucrose alone solution. Early neonatal fentanyl exposure did not significantly alter fentanyl intake or nose-poke response. In contrast, early fentanyl exposure did alter thermal antinociception in both male and female rats. Specifically, fentanyl (10 μg/kg) pre-treatment increased baseline paw-lick latencies, and the higher dose of fentanyl (100 μg/kg) reduced morphine-induced paw-lick latencies. Fentanyl pre-treatment did not alter U50,488-mediated thermal antinociception.ConclusionsAlthough our exposure model is not reflective of typical human fentanyl use during pregnancy, our study does illustrate that even brief exposure to fentanyl during early development can have long-lasting effects on mu-opioid-mediated behavior. Moreover, our data suggest that females may be more susceptible to fentanyl abuse than males.

show abstract

Section: Introductionmentioning

confidence: 99%

Effects of neonatal fentanyl on late adolescent opioid-mediated behavior

Crawford

Taylor²,

Park³

et al. 2023

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

Development of Paediatric Medicines: Key Risk Factors and Non-clinical Research Programmes

Енгалычева¹,

Subaev²

2023

Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo pr

View full text Add to dashboard Cite

The lack of approved paediatric medicines is a global problem. Since paediatric patients are a high-risk group, a developer of paediatric medicines needs to evaluate and minimise unjustified risks early in the development process.The aim of the study was to analyse the current regulatory and methodological framework for non-clinical research and identify key risk factors that need addressing in paediatric drug development in order to substantiate the safety of children. One of the main objectives of non-clinical safety assessment of a medicinal product intended for children is to identify undesirable effects on child growth and development. According to national and international methodological guidelines, the developer may obtain the most valuable information to decide whether it is safe to enrol children into a clinical trial from the safety data collected in clinical studies in adult subjects. If the safety data available from studies in mature animals and adult subjects are insufficient to evaluate the safety of the clinical trial for paediatric patients, the developer may consider conducting non-clinical studies in immature (juvenile) animals. A paediatric non-clinical testing programme should be in line with a comprehensive significance assessment of key risk factors carried out on a case-by-case basis using the weight-of-evidence (WoE) analysis. The conclusion on the safety of a medicinal product for children should be based on risk assessment in relevant clinical and non-clinical studies.

show abstract

Considerations for and against dosing rodent pups before 7 days of age in juvenile toxicology studies

Cited by 2 publications

References 83 publications

Effects of neonatal fentanyl on late adolescent opioid-mediated behavior

Effects of neonatal fentanyl on late adolescent opioid-mediated behavior

Development of Paediatric Medicines: Key Risk Factors and Non-clinical Research Programmes

Contact Info

Product

Resources

About