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

Malek Antoine, Obrist Cristina, Wenzinger Silvana, Von

Description

Methadone is the therapeutic agent of choice for the treatment of opiate addiction in pregnancy. The co-consumption (heroin, cocaine) which may influence the effects of methadone is frequent. Therefore, the impact of cocaine and heroin on the placental transfer of methadone and the placental tissue was investigated under in vitro conditions. Methods Placentae (n = 24) were ex-vivo perfused with medium (m) (control, n = 6), m plus methadone (n = 6), m plus methadone and cocaine (n = 6) or m plus methadone and heroin (n = 6). Placental functionality parameters like antipyrine permeability, glucose consumption, lactate production, hormone production (hCG and leptin), microparticles release and the expression of P-glycoprotein were analysed. Results Methadone accumulated in placental tissue. Methadone alone decreased the transfer of antipyrine from 0.60 +/- 0.07 to 0.50 +/- 0.06 (fetal/maternal ratio, mean +/- SD, P < 0.01), whereas the combination with cocaine or heroin increased it (0.56 +/- 0.08 to 0.68 +/- 0.13, P = 0.03 and 0.58 +/- 0.21 to 0.71 +/- 0.24; P = 0.18). Microparticles (MPs) released from syncytiotrophoblast into maternal circuit increased by 30% after cocaine or heroin (P < 0.05) and the expression of P-glycoprotein in the tissue increased by ≥ 49% after any drug (P < 0.05). All other measured parameters did not show any significant effect when methadone was combined with cocaine or heroine. Conclusion The combination of cocaine or heroin with methadone increase antipyrine permeability. Changes of MPs resemble findings seen in oxidative stress of syncytiotrophoblast.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2009
• Nombre de lectures: 5
• Langue: English

Extrait

Reproductive Biology and Endocrinology

BioMedCentral

Open Access Research The impact of cocaine and heroin on the placental transfer of methadone Antoine Malek*, Cristina Obrist, Silvana Wenzinger and Ursula von Mandach*

Address: Department of Obstetrics, Zurich University Hospital, Frauenklinikstr. 10, 8091 Zurich, Switzerland Email: Antoine Malek*  [e-mail]; Cristina Obrist  [e-mail]; Silvana Wenzinger  [e-mail]; Ursula von Mandach*  [e-mail] * Corresponding authors

Published: 11 June 2009 Received: 28 March 2009 Accepted: 11 June 2009 Reproductive Biology and Endocrinology2009,7:61 doi:10.1186/14777827761 This article is available from: http://www.rbej.com/content/7/1/61 © 2009 Malek et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background:Methadone is the therapeutic agent of choice for the treatment of opiate addiction in pregnancy. The coconsumption (heroin, cocaine) which may influence the effects of methadone is frequent. Therefore, the impact of cocaine and heroin on the placental transfer of methadone and the placental tissue was investigated under in vitro conditions. Methods:Placentae (n = 24) were exvivo perfused with medium (m) (control, n = 6), m plus methadone (n = 6), m plus methadone and cocaine (n = 6) or m plus methadone and heroin (n = 6). Placental functionality parameters like antipyrine permeability, glucose consumption, lactate production, hormone production (hCG and leptin), microparticles release and the expression of Pglycoprotein were analysed. Results:Methadone accumulated in placental tissue. Methadone alone decreased the transfer of antipyrine from 0.60 +/ 0.07 to 0.50 +/ 0.06 (fetal/maternal ratio, mean +/ SD, P < 0.01), whereas the combination with cocaine or heroin increased it (0.56 +/ 0.08 to 0.68 +/ 0.13, P = 0.03 and 0.58 +/ 0.21 to 0.71 +/ 0.24; P = 0.18). Microparticles (MPs) released from syncytiotrophoblast into maternal circuit increased by 30% after cocaine or heroin (P < 0.05) and the expression of P glycoprotein in the tissue increased by≥after any drug (P < 0.05). All other measured 49% parameters did not show any significant effect when methadone was combined with cocaine or heroine. Conclusion:The combination of cocaine or heroin with methadone increase antipyrine permeability. Changes of MPs resemble findings seen in oxidative stress of syncytiotrophoblast.

Background In developed countries an increase in substance abuse in pregnancy can be observed. Opiates cross the placenta easily and lead to intrauterine growth restriction (IUGR), preterm birth and spontaneous abortion [14]. Absti nence cannot be achieved in most of the patients and

methadone is the recommended standard of care for preg nant opioiddependent women [5]. The positive effects of methadone are an increase in birth weight and the prolon gation of gestation [4,6]. In addition, women in a mainte nance therapy program receive more prenatal care which improves the situation for both, mother and fetus. How

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