Transplacental passage of lamotrigine in a human placental perfusion system in vitro and in maternal and cord blood in vivo.
ABSTRACT We studied transplacental passage of lamotrigine (3,5-diamino-6-[2,3-dichlorophenyl]-1,2,4-triazine; LTG) using an ex vivo human placental perfusion method and in in vivo samples.
Term placentas from healthy mothers without medications were perfused in a recirculating dual perfusion system. LTG (2.5 microg/ml, n=4; 10 microg/ml, n=4) and reference compound antipyrine (100 microg/ml) were added into the maternal circulation. The disappearance of drugs from the maternal circulation and appearance into the foetal circulation was followed every 15 min up to 2 h. Drug concentrations were analysed using high-performance liquid chromatography. In addition to human placental perfusions, we analysed LTG concentrations in maternal vein and cord blood samples after delivery from two epileptic mothers receiving LTG therapy during pregnancy.
LTG was detectable in the foetal circulation at 15 min in all of the perfusions, indicating rapid transfer. Maternal and foetal concentrations reached equilibrium at 60 min with both concentrations used. The feto-maternal ratio was 1.26+/-0.20 with 10 microg/ml LTG and 0.83+/-0.41 with 2.5 microg/ml LTG at the end of the perfusion. The transfer of LTG from the maternal to the foetal compartment at 120 min was 28.9+/-10.7% with 2.5 microg/ml LTG and 37.8+/-3.2% with 10 microg/ml LTG (p>0.05). In the serum samples from epileptic mothers, the cord blood maternal concentration ratio was 1.02 in one pair and 1.55 in the other.
LTG crossed the placenta easily and rapidly, indicating that the maternal treatment leads to a considerable foetal exposure.
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ABSTRACT: Many mothers use, against instructions, alcohol during pregnancy. Simultaneously mothers are exposed to a wide range of other environmental chemicals. These chemicals may also harm the developing fetus, because almost all toxic compounds can go through human placenta. Toxicokinetic effects of ethanol on the transfer of other environmental compounds through human placenta have not been studied before. It is known that ethanol has lytic properties and increases the permeability and fluidity of cell membranes. We studied the effects of ethanol on the transfer of three different environmental toxins: nicotine, PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine) and NDMA (N-nitrosodimethylamine) in placental perfusion. We tested in human breast cancer adenocarcinoma cell line MCF-7 whether ethanol affects ABCG2/BCRP, which is also the major transporter in human placenta. We found that the transfer of ethanol is comparable to that of antipyrine, which points to passive diffusion as the transfer mechanism. Unexpectedly, ethanol had no statistically significant effect on the transfer of the other studied compounds. Neither did ethanol inhibit the function of ABCG2/BCRP. These experiments represent only the effects of acute exposure to ethanol and chronic exposure remains to be studied.Toxicology Letters 06/2011; 205(3):257-64. DOI:10.1016/j.toxlet.2011.06.014 · 3.36 Impact Factor
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ABSTRACT: 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.Drug Metabolism Reviews 02/2007; 39(4):723-46. DOI:10.1080/03602530701690390 · 6.29 Impact Factor