Piperaquine phosphate: reproduction studies.

In embryofetal studies in rat and rabbit Piperaquine phosphate (PQP) was not teratogenic at the maximal tolerated dose, even in presence of fetal exposure. In peri- post-natal study in rat, PQP did not interfere with the course of delivery at the dose of 5 mg/kg/day (treatment Gestation Day(GD)6-Lactation Day(LD)21) as well as up to the dose of 20 mg/kg/day (treatment GD6-17 and LD1-21). PQP at the dose of 80 mg/kg, induced prolonged gestation, dystocic delivery and increase perinatal mortality both with interruption of treatment (GD6 to GD17 and LD1-21) and with continuous dosing (GD19-LD21).

Comparative embryotoxicity of different antimalarial peroxides: in vitro study using the rat whole embryo culture model (WEC).

Three groups of compounds: (i) active peroxides (artemisinin and arterolene), (ii) inactive non-peroxidic derivatives (deoxyartemisinin and carbaOZ277) and (iii) inactive peroxide (OZ381) were tested by WEC system to provide insights into the relationship between chemical structure and embryotoxic potential, and to assess the relationship between embryotoxicity and antimalarial activity. Deoxyartemisinin, OZ381 and carbaOZ277 did not affect rat embryonic development. Artemisinin and arterolane affected primarily nucleated red blood cells (RBCs), inducing anemia and subsequent tissue damage in rat embryos, with NOELs for RBC damage at 0.

Investigations of the effects of the antimalarial drug dihydroartemisinin (DHA) using the Frog Embryo Teratogenesis Assay-Xenopus (FETAX).

Artemisinin derivatives are effective and safe drugs for treating malaria, but they are not recommended during the first trimester of pregnancy because of resorptions and abnormalities observed in animal reproduction studies. Previous studies in rats showed that artemisinin embryotoxicity derives from the depletion of primitive red blood cells (RBCs) over a narrow critical time window (gestation Days 9-14). In order to further investigate the susceptibility of primitive RBCs to artemisinins and to establish whether this susceptibility is species-specific or inherent to the compound, we studied dihydroartemisinin (DHA), both a drug in its own right and the main metabolite of current artemisinin derivatives in use, in the Frog Embryo Teratogenesis Assay-Xenopus (FETAX).

Assessing and managing toxicities induced by kinase inhibitors.

Currently, several protein kinase-modulating compounds have received market approval across a range of diverse therapeutic indications. Furthermore, a large number of chemical and biological protein kinase-modulating compounds are undergoing testing at the preclinical and clinical level. Protein kinases are both major pharmacological targets and diagnostically useful.

In vivo and in vitro investigations of the effects of the antimalarial drug dihydroartemisinin (DHA) on rat embryos.

Artemisinin derivatives are clinically effective and safe antimalarials, but are not recommended during the first trimester of pregnancy because of the resorptions and abnormalities seen in animal reproduction studies. Understanding how, when and what toxicity occurs is crucial to any assessment of clinical relevance. Previously, DHA has been shown in the rat whole embryo culture (WEC) to primarily affect primitive red blood cells (RBCs) causing subsequent tissue damage and dysmorphogenesis.

Effects of the antimalarial drug dihydroartemisinin (DHA) on rat embryos in vitro.

Artemisinin derivatives are not currently recommended for use during the first trimester of pregnancy because they cause embryo death and some abnormalities in early pregnancy in animals. We studied the effects of dihydroartemisinin (DHA) in rat whole embryo cultures (WEC). DHA was added to the culture medium for the entire 48-h culture, 1.