Disposition of stiripentol in the pregnant and non-pregnant female rat

Abstract

1. The disposition of stiripentol labelled with ¹⁴C and ³H on two positions has been studied in the pregnant and non-pregnant female rat after p.o. administration of a 200 mg/kg dose.

2. For both labelled species radioactivity was eliminated mainly in the faeces (69% within 72 h). Urinary excretion was rather low (22% within 72 h). No significant difference was found between the disposition of the two labelled species.

3. For both labelled species concentrations of radioactivity reached a plateau in the plasma and tissues between 1 and 6 h after administration. The liver, fat, mammary gland and adrenal gland were the most extensively-labelled organs. The affinity for the mammary gland was significatively greater in pregnant rats and for the adrenal gland was significantly greater in the non-pregnant rats. The fact that the concentration in the placenta was higher than in the foetus demonstrated that this membrane acts as a barrier for the penetration of the drug in the amniotic fluid.

4. Chromatographic analysis of the faeces and urine showed that an important portion of the dose remained unabsorbed through the gastrointestinal tract. The absorbed fraction undergoes an extensive first-pass metabolism involving mainly the oxidative cleavage of the methylenedioxy ring. Comparison with the results of other work conducted on the non-pregnant rat demonstrated that pregnancy did not affect the disposition and metabolic process.