Placental Transfer of Phenobarbitone in Epileptic Women, and Elimination in Newborns

Melchior, J. C.; Svensmark, Ole; Trolle, Dyre

doi:10.1016/s0140-6736(67)92593-7

Cited by 82 publications

(22 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is clear that all the currently used antiepileptic drugs can readily cross placenta (Kumar et al, 2000;Melchior et al, 1967;Myllynen et al, 2003;Pienimaki et al, 1995;Staud et al, 1997). To date, there is lack of study for roles of the drug transporter proteins in their transplacental passage or the potential genetic influence of transporter polymorphisms on their fetal drug exposure.…”

Section: Antiepilepticsmentioning

confidence: 99%

The Emerging Importance of Transporter Proteins in the Psychopharmacological Treatment of the Pregnant Patient

Wang

Newport

Stowe

et al. 2007

Drug Metabolism Reviews

View full text Add to dashboard Cite

P-glycoprotein, breast cancer resistance protein, and multidrug resistance proteins have physiological functions in placental tissue. Several antidepressants, antipsychotics, and anti-epileptic drugs have been found to be substrates of P-glycoprotein and other transporters. The extent that drugs pass through the placental barrier is likely influenced by drug transporters. The rational choice of psychoactive drugs to treat mental illness in women of child-bearing age should incorporate knowledge of both drug disposition as well as expected pharmacologic effects. This review summarizes the current data on drug transporters in the placental passage of medications, with a focus on medications used in clinical psychopharmacology.

show abstract

Section: Antiepilepticsmentioning

confidence: 99%

The Emerging Importance of Transporter Proteins in the Psychopharmacological Treatment of the Pregnant Patient

Wang

Newport

Stowe

et al. 2007

Drug Metabolism Reviews

View full text Add to dashboard Cite

show abstract

“…Peak concentrations in fetuses are two-thirds of peak maternal plasma concentrations. In humans, by contrast, phenobarbital concentrations in maternal and cord plasma at term are comparable (Melchior et al, 1967;Nau et al, 1980Nau et al, , 1982Ishizaki et al, 1981;DeCarolis et al, 1992). The drug is proteinbound to a small extent in both the fetus (36 -43%) and the adult (45%) (Nau et al, 1982), suggesting that protein binding is relatively unimportant in maternal-fetal distribution of this drug.…”

Section: Phenobarbitalmentioning

confidence: 99%

Mechanisms regulating toxicant disposition to the embryo during early pregnancy: An interspecies comparison

Carney

Scialli²,

Watson

et al. 2004

Birth Defects Research Pt C

View full text Add to dashboard Cite

The dose of toxicant reaching the embryo is a critical determinant of developmental toxicity, and is likely to be a key factor responsible for interspecies variability in response to many test agents. This review compares the mechanisms regulating disposition of toxicants from the maternal circulation to the embryo during organogenesis in humans and the two species used predominantly in regulatory developmental toxicity testing, rats and rabbits. These three species utilize fundamentally different strategies for maternal-embryonic exchange during early pregnancy. Early postimplantation rat embryos rely on the inverted visceral yolk sac placenta, which is in intimate contact with the uterine epithelium and is equipped with an extensive repertoire of transport mechanisms, such as pinocytosis, endocytosis, and specific transporter proteins. Also, the rat yolk sac completely surrounds the embryo, such that the fluid-filled exocoelom survives through most of the period of organogenesis, and can concentrate compounds such as certain weak acids due to pH differences between maternal blood and exocelomic fluid. The early postimplantation rabbit conceptus differs from the rat in that the yolk sac is not closely apposed to the uterus during early organogenesis and does not completely enclose the embryo until relatively later in development (approximately GD13). This suggests that the early rabbit yolk sac might be a relatively inefficient transporter, a conclusion supported by limited data with ethylene glycol and one of its predominant metabolites, glycolic acid, given to GD9 rabbits. In humans, maternal-embryo exchange is thought to occur via the chorioallantoic placenta, although it has recently been conjectured that a supplemental route of transfer could occur via absorption into the yolk sac. Knowledge of the mechanisms underlying species-specific embryonic disposition, factored together with other pharmacokinetic characteristics of the test compound and knowledge of critical periods of susceptibility, can be used on a case-by-case basis to make more accurate extrapolations of test animal data to the human.

show abstract

“…In newborns of epileptic mothers, neonatal phénobarbital blood levels of 100 ± 30 [1], 95 ± 3 [19] and 84 ± 19% [20] with respect to maternal levels have been reported. Skankaran et al [13] found values of 105 ± 20% in infants of mothers treated for the prevention of neonatal intracerebral hemorrhage.…”

Section: Discussionmentioning

confidence: 98%

Placental Transfer of Phenobarbital: What Is New?

Carolis¹,

Romagnoli²,

Frezza³

et al. 1992

Dev Pharmacol Ther

View full text Add to dashboard Cite

The placental transfer of phénobarbital was investigated in 35 mother-infant pairs at birth. The drug was administered prenatally to the mothers for maternal epilepsy (group 1, n = 5), gestational hypertension and preeclampsia (group 2, n = 20) and prophylaxis of intraventricular hemorrhage in premature deliveries (group 3, n = 10). The phénobarbital levels in arterial cord blood were 100 ± 2.8% in group 1, 89 ± 21% in group 2 and 77 ± 16% in group 3 with respect to the levels observed in the mothers. The most important factor influencing the transplacental passage was the duration of maternal treatment in the infant of group 1 (r = 0.80, p < 0.01), the gestational age in the infants of group 2 (r = 0.74, p < 0.01) and the arterial cord pH in the infants of group 3 (r = 0.89, p < 0.001).

show abstract

Placental Transfer of Phenobarbitone in Epileptic Women, and Elimination in Newborns

Cited by 82 publications

References 10 publications

The Emerging Importance of Transporter Proteins in the Psychopharmacological Treatment of the Pregnant Patient

The Emerging Importance of Transporter Proteins in the Psychopharmacological Treatment of the Pregnant Patient

Mechanisms regulating toxicant disposition to the embryo during early pregnancy: An interspecies comparison

Placental Transfer of Phenobarbital: What Is New?

Contact Info

Product

Resources

About