Influence of protein-calorie malnutrition on the pharmacokinetics, placental transfer and tissue localization of dexamethasone in rats

Abstract

1 The influence of protein-calorie malnutrition (PCM) on the pharmacokinetics, transplacental passage and tissue localization of dexamethasone was determined in Sprague-Dawley rats. 2 PCM increased the plasma half-life and volume of distribution of dexamethasone in pregnant but not in nonpregnant rats. 3 Ratios of foetal to maternal serum dexamethasone concentrations were 0.2–0.4 at different dose levels (0.8–20 μmol kg⁻¹), time intervals (0.25–12 h) and gestational ages (day 14–21). 4 PCM increased the foetal serum and tissue concentrations of dexamethasone but exerted no significant effect on its binding to maternal and foetal serum proteins or on its metabolism by the placenta. 5 It is suggested that significantly lower foetal than maternal serum levels of dexamethasone are due to efficient elimination of this agent by the foeto-placental unit and an impairment of this mechanism may account for the observed increase in dexamethasone levels in the foetuses of PCM rats.