Embryo-fetal development toxicity of carenoprazan hydrochloride / 中国药科大学学报

@#Carenoprazan has the similar structure and mechanism with the potassium-competitive blocker vonoprazan. Howerver, its safety during the pregnancy remains uncertain. To study the embryo-fetal development toxicity and toxicokinetics of carenoprazan hydrochloride via oral administration, time-mated Sprague-Dawley rats were divided into 5 groups, treated with normal saline, cyclophosphamide for injection(3. 8 mg/kg), and carenoprazan hydrochloride(20, 60, 200 mg/kg), respectively. Administrated orally from gestation day(GD)6 - 15. At the termination(GD 20), pregnant dams were sacrificed, and concentrations of carenoprazan hydrochloride as well as its metabolite in plasma and issues of both maternal and fetus were examined. As a result, the body weight gain of maternal in both high(200 mg/kg)and medium(60 mg/kg)dose as well as the food consumption of high-dose were decreased during GD 10-16. At the high dose group, decrease of crown rump length of fetuses were significant. Also, skeletal malformation/variations of fetus increased obviously at both high- and medium- dosage. The toxcicokinetics of carenoprazan hydrochloride are linear after single treatment between 20-200 mg/kg. The placental barrier was penetrated by carenoprazan hydrochloride and metabolite, and the distribution of metabolite in organs were similar in both maternal and fetus, with the highest concentration in livers. Therefore might resulted in the development toxicity. The No Observed Adverse Effect Level(NOAEL)of carenoprazan hydrochloride for both maternal and fetal was 20 mg/kg.

Study on skin irritation and allergenicity by indomethacin emulsion / 药学实践杂志

Objective Study on skin irritation and allergenicity of indomethacin emulsion ,in order to provide theoretical basis for clinical safe medication .Methods New Zealand white rabbits were used to test skin irritation ,given 0 .5g test sub-stance for 14 days .The skin irritation was observed in the two groups with eight rabbits each during the experiment .Six rab-bits in each group were sacrificed 72 hours after the last medication and skin tissues were taken for histopathology examination ;and the skin tissues of remaining two rabbits were taken for histopathology examination in 14th day after the last medication . Guinea pigs were used to test skin allergenicity ,given 0 .5g test substance on day 0 ,7 ,14 for local induction .On day 28 ,the animal subjects were given 0 .4g test substance on non-administration skin of guinea pigs for local excitation .Results Slight ir-ritation of indomethacin emulsion on normal or damaged skin was observed but it is reversible after withdrawal for rabbits .Sen-sitization effect on the skin of guinea pig was not found .Conclusion Indomethacin emulsion is not suitable to long-term use clinically ,and skin irritation need to pay more attention .