Investigation of the maternal to foetal serum concentration gradient of dexamethasone in the rat

Abstract

The basis of the maternal to foetal serum concentration gradient of dexamethasone was investigated in the rat on day 20 of gestation. The pregnant rat was assumed to behave as a two‐compartment open model with one maternal and one foetal pool exchanging with each other and each to outside. Bolus injections of unlabelled dexamethasone were made into the mother and of [3H]‐dexameth‐asone into its foetuses and serial maternal and foetal blood samples were collected a number of times. The monitoring of both forms of the drug in each sample permitted the estimation by a non‐linear least square approach of two placental and two non‐placental clearances. After both maternal and foetal injections of dexamethasone, its concentrations were higher in the maternal than in the foetal serum. Placental clearance of dexamethasone from the foetus to the mother was 824 ± 40 ml kg−1 h−1 and 8.5 ± 1 times greater than the placental clearance from the mother to foetus (103 ± 2 ml kg−1 h−1). Foetal non‐placental clearance was zero. It is suggested that a maternal to foetal serum gradient of dexamethasone is caused by its active transfer from the foetal to maternal side. 1986 British Pharmacological Society