Related Experiment Video
Updated: Aug 15, 2026
08:08
Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the ex vivo Human Placental Perfusion Model
Published on: June 18, 2013
Bidirectional transfer of methadone across human placenta
Ilona A Nekhayeva1, Tatiana N Nanovskaya, Sujal V Deshmukh
1Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555 0587, USA.
Biochemical Pharmacology
|December 14, 2004
Summary
Methadone transfer across the placenta is asymmetric, with higher fetal to maternal transfer. This placental disposition may influence neonatal abstinence syndrome severity in infants exposed to methadone during pregnancy.
Area of Science:
- Pharmacology
- Obstetrics
- Neonatology
Background:
- Methadone maintenance is standard care for pregnant opioid users.
- Limited data exist on methadone pharmacokinetics during pregnancy, especially placental transfer.
Purpose of the Study:
- To investigate the bidirectional transfer of methadone across the human placenta.
- To assess methadone's effects on placental viability and function.
- To explore the role of placental disposition in fetal methadone exposure.
Main Methods:
- Dual perfusion of term placental lobules.
- In vitro assessment of methadone transfer and placental parameters.
- Measurement of methadone concentrations in maternal and fetal circulation simulations.
Main Results:
- Methadone did not adversely affect placental viability or function.
- Methadone was retained by placental tissue.
- Asymmetric transfer observed: fetal to maternal clearance index (0.97±0.05) was significantly higher than maternal to fetal (0.83±0.09).
- P-glycoprotein (P-gp) efflux transporter activity likely explains the asymmetric transfer.
Conclusions:
- Placental disposition of methadone is significant and asymmetric.
- P-glycoprotein activity influences fetal methadone exposure.
- Placental transfer may regulate fetal methadone levels, impacting neonatal abstinence syndrome.
Related Concept Videos
01:15Transcytosis of IgG
Transcytosis is the process in which molecules are internalized by endocytosis, transported across the cell, and released through exocytosis from the opposite end of the cell. Molecules such as insulin, immunoglobulins, and certain nutrients are transferred through the recycling endosomes by recycling and transcytosis.
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
01:25Physiological Barriers
Physiological barriers are semi-permeable cellular structures restricting drug diffusion into intracellular compartments and tissues. There are six types of physiological barriers: blood endothelial, cell membrane, blood-brain, blood-cerebrospinal fluid (CSF), blood-placenta, and blood-testis barriers.
The blood endothelial barrier is the most porous of these. It allows all small ionized, un-ionized, and lipophilic molecules to pass through the endothelial lining into the interstitial space...
The blood endothelial barrier is the most porous of these. It allows all small ionized, un-ionized, and lipophilic molecules to pass through the endothelial lining into the interstitial space...
01:23Factors Affecting Drug Distribution: Physiological Barriers
Drug distribution in the body is intricately regulated by various physiological barriers that control the passage of substances. These include the capillary endothelial barrier, the blood-brain, blood-cerebrospinal fluid, blood-placental, and blood-testis barriers.
The capillary endothelial barrier allows only smaller molecules below 600 Da (Daltons) to pass through. It also restricts drugs like heparin that are bound to blood components, limiting their movement within the bloodstream.
The...
The capillary endothelial barrier allows only smaller molecules below 600 Da (Daltons) to pass through. It also restricts drugs like heparin that are bound to blood components, limiting their movement within the bloodstream.
The...
01:17Phase II Reactions: Methylation Reactions
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
01:24Drug Accumulation During Multiple Dosing: Intermittent IV Infusions
Intermittent intravenous (IV) infusion is a method of drug administration where medications are delivered over short infusion periods followed by intervals of no drug delivery. This approach helps to prevent sustained high drug concentrations in the bloodstream, reducing the risk of adverse effects associated with prolonged exposure. Unlike continuous infusion, steady-state concentrations may not be achieved during a single dosing cycle but can be reached through repeated...
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...