Reproductive toxicology
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Reproductive toxicology · Aug 2015
ReviewEndothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension.
The Pregnancy Prevention Program (PPP) is in place to prevent drug-induced developmental malformations. Remarkably, among the ten PPP-enlisted drugs are three endothelin-1 (ET-1) receptor antagonists (ERA's: ambrisentan, bosentan and macitentan), which are approved for the treatment of Pulmonary Arterial Hypertension (PAH). ⋯ While ERA's hamper pathological remodeling of the pulmonary vasculature and as such exert beneficial effects in PAH, they disturb fetal development of cardiopulmonary tissues. By blocking ET-1-mediated positive inotropic effects and myocardial fetal gene induction, ERA's may affect right ventricular adaptation to the increased pulmonary vascular resistance in both the fetus and the adult PAH patient.
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Reproductive toxicology · Aug 2015
ReviewUse of juvenile animal studies to support oncology medicine development in children.
Childhood cancer has remained a challenge because of long-term effects in children. The need to extend access of children into new cancer therapies requires early prediction of specific safety aspects and juvenile animal studies (JAS) are being conducted to screen for age-related toxicities and differences occurring during postnatal development. ⋯ For 6 of the cancer medicines with JAS the toxicity profile in adult and juvenile animals showed some differences in study findings. The discussion of these cases is illustrative of the potential significance that JAS have provided in oncology medicines.