Reproduction study of propiverine hydrochloride (4)--perinatal and postnatal study in rats by oral administration

Abstract

A perinatal and postnatal study was performed in Sprague-Dawley rats by oral administration of propiverine hydrochloride (P-4) at dose levels of 0 (control), 2, 10 and 50 mg/kg/day to dams from day 17 of pregnancy to day 21 after delivery. Twenty two or twenty four dams in each group were allowed to deliver for the postnatal examination of their offspring. In dams, the dose of 50mg/kg caused toxic signs consisting of mydriasis, salivation and rale. One dam of this group showed piloerection, low body temperature, blanching of extremity and auricle, and emaciation associated with marked prolongation of delivery. Body weight gain of the dams was retarded in the 50 mg/kg group throughout the administration period. Food and water intakes were reduced in the 50mg/kg group. In gross pathology of the dam that showed prolonged delivery, the spleen and thymus were moderately or severely atrophied and the adrenal was moderately enlarged. The viability index of the offspring on day 4 was reduced in the 50mg/kg group. Body weight of pups slightly decreased in the 50mg/kg group during sucking and rearing periods. Absolute weights of some organs of the three-week aged offspring were reduced due to attributable depression of body weight gain. However, P-4 had no adverse effect on the postnatal development such as emotionality, motor activity, learning ability or reproductive performance. The results suggest that the non-effective dose level of P-4 is 10mg/kg/day in maternal animals and offspring.