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[Benzodiazepines and pregnancy. Transplacental passage, labor and lactation]
Benzodiazepines (BZD) are lipophilic molecules, undissociated agents which easily penetrate membranes. Pharmacokinetics of BZD arises from these chemico-physical properties. Thus BZD show a rapid placental transfer with significant uptake of the drug, in both early and late pregnancy. The changes in the placental structures and in the circulation of the uterus during pregnancy are responsible in the greater placental passage in late pregnancy. After repeated doses in pregnant women, BZD tend to accumulate on the fetus, and the " flappy infant" syndrome may occur. The disposition of diazepam in women to the end of the pregnancy is altered. The terminal half-life is about twice as in non pregnant control, the distribution volume is increased but the total plasma clearance is not changed. In neonate child and particularly in premature infant, elimination of the BZD is slower in relation with immaturity of the hepatic enzymes systems metabolising drugs. BZD appear in human milk, but only high clinical doses might be expected to exert an effect on the nursing newborn. In the first trimester of pregnancy use of BZD has to be exceptional; the safety of these products in early pregnancy has not yet been definitively established. In the late pregnancy and at the parturition, there are more clear indications. Generally high single doses and repeated and prolonged administrations have to be avoided.
Benzodiazepines (BZD) are lipophilic molecules, undissociated agents which easily penetrate membranes. Pharmacokinetics of BZD arises from these chemico-physical properties. Thus BZD show a rapid placental transfer with significant uptake of the drug, in both early and late pregnancy. The changes in the placental structures and in the circulation of the uterus during pregnancy are responsible in the greater placental passage in late pregnancy. After repeated doses in pregnant women, BZD tend to accumulate on the fetus, and the " flappy infant" syndrome may occur. The disposition of diazepam in women to the end of the pregnancy is altered. The terminal half-life is about twice as in non pregnant control, the distribution volume is increased but the total plasma clearance is not changed. In neonate child and particularly in premature infant, elimination of the BZD is slower in relation with immaturity of the hepatic enzymes systems metabolising drugs. BZD appear in human milk, but only high clinical doses might be expected to exert an effect on the nursing newborn. In the first trimester of pregnancy use of BZD has to be exceptional; the safety of these products in early pregnancy has not yet been definitively established. In the late pregnancy and at the parturition, there are more clear indications. Generally high single doses and repeated and prolonged administrations have to be avoided.