The impact of cocaine and heroin on the placental transfer of methadone

Malek, Antoine; Obrist, Cristina; Wenzinger, Silvana; Mandach, Ursula von

doi:10.1186/1477-7827-7-61

Cited by 50 publications

(35 citation statements)

References 43 publications

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“…So, in case of missing abstinence during pregnancy a replacement therapy with methadone is recommended. The ex vivo human placental perfusion model revealed that the transfer of methadone into the fetal circulation is negligible 11 , which correlates well with the calculated cord blood-to-maternal blood concentration ratio after delivery 12 .…”

Section: Introductionmentioning

confidence: 57%

“…Further representative results obtained with the ex vivo dual recirculating human placental perfusion model were published recently 11,19 . 19 .…”

Section: Representative Resultsmentioning

confidence: 99%

“…The ex vivo dual recirculating human placental perfusion model provides a controlled and reliable system for studying the placental transport of various endogenous and exogenous compounds 3,11,12,18,19 and a wide range of other functions of the placenta like mechanisms responsible for the development of pathological states like preeclampsia [20][21][22] . In this protocol we focus mainly on the set up, handling and method that allow the study of accumulation, effects and translocation rates of a broad set of xenobiotics or nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

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Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the <em>ex vivo</em> Human Placental Perfusion Model

Grafmüller

Manser

Krug

et al. 2013

JoVE

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Decades ago the human placenta was thought to be an impenetrable barrier between mother and unborn child. However, the discovery of thalidomide-induced birth defects and many later studies afterwards proved the opposite. Today several harmful xenobiotics like nicotine, heroin, methadone or drugs as well as environmental pollutants were described to overcome this barrier. With the growing use of nanotechnology, the placenta is likely to come into contact with novel nanoparticles either accidentally through exposure or intentionally in the case of potential nanomedical applications. Data from animal experiments cannot be extrapolated to humans because the placenta is the most species-specific mammalian organ 1 . Therefore, the ex vivo dual recirculating human placental perfusion, developed by Panigel et al. in 1967 2 and continuously modified by Schneider et al. in 1972 3 , can serve as an excellent model to study the transfer of xenobiotics or particles.Here, we focus on the ex vivo dual recirculating human placental perfusion protocol and its further development to acquire reproducible results.The placentae were obtained after informed consent of the mothers from uncomplicated term pregnancies undergoing caesarean delivery. The fetal and maternal vessels of an intact cotyledon were cannulated and perfused at least for five hours. As a model particle fluorescently labelled polystyrene particles with sizes of 80 and 500 nm in diameter were added to the maternal circuit. The 80 nm particles were able to cross the placental barrier and provide a perfect example for a substance which is transferred across the placenta to the fetus while the 500 nm particles were retained in the placental tissue or maternal circuit. The ex vivo human placental perfusion model is one of few models providing reliable information about the transport behavior of xenobiotics at an important tissue barrier which delivers predictive and clinical relevant data. Video LinkThe video component of this article can be found at

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Section: Introductionmentioning

confidence: 57%

“…Further representative results obtained with the ex vivo dual recirculating human placental perfusion model were published recently 11,19 . 19 .…”

Section: Representative Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the <em>ex vivo</em> Human Placental Perfusion Model

Grafmüller

Manser

Krug

et al. 2013

JoVE

Self Cite

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“…72 The combination of cocaine or heroin with methadone further increases the permeability of methadone across the placenta. 73 Together, the ease with which these drugs can cross the bloodbrain barrier of the fetus, and the prolonged half-life of these drugs in the fetus, 74 may worsen the withdrawal in infants. Neonatal abstinence syndrome is the end result of the sudden discontinuation of prolonged fetal exposure to opioids.…”

Section: Pathophysiologymentioning

confidence: 99%

Neonatal Abstinence Syndrome

2014

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Neonatal abstinence syndrome (NAS) is a result of the sudden discontinuation of fetal exposure to substances that were used or abused by the mother during pregnancy. Withdrawal from licit or illicit substances is becoming more common among neonates in both developed and developing countries. NAS continues to be an important clinical entity throughout much of the world. NAS leads to a constellation of signs and symptoms involving multiple systems. The pathophysiology of NAS is not completely understood. Urine or meconium confirmation may assist the diagnosis and management of NAS. The Finnegan scoring system is commonly used to assess the severity of NAS; scoring can be helpful for initiating, monitoring, and terminating treatment in neonates. Nonpharmacological care is the initial treatment option, and pharmacological treatment is required if an improvement is not observed after nonpharmacological measures or if the infant develops severe withdrawal. Morphine is the most commonly used drug in the treatment of NAS secondary to opioids. An algorithmic approach to the management of infants with NAS is suggested. Breastfeeding is not contraindicated in NAS, unless the mother is taking street drugs, is involved in polydrug abuse, or is infected with HIV. Future studies are required to assess the long-term effects of NAS on children after prenatal exposure.

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“…The P-gp is an efflux transporter meaning the protection of the placenta and the fetus against many drugs [87,88]. In a second perfusion study [89], the effect of the combined cocaine plus methadone on the placental function was investigated. All tested compounds were added to the maternal circulation.…”

Section: Impact Of Cocaine On Placental Functionmentioning

confidence: 99%