The impact of cocaine and heroin on the placental transfer of methadone.
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 >or= 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.


CONCLUSIONS
The combination of cocaine or heroin with methadone increase antipyrine permeability. Changes of MPs resemble findings seen in oxidative stress of syncytiotrophoblast.
Malek
Antoine
A
Department of Obstetrics, Zurich University Hospital, Frauenklinikstr, 10, 8091 Zurich, Switzerland. antoine.malek1@gmail.com
Obrist
Cristina
C
Wenzinger
Silvana
S
von Mandach
Ursula
U
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000983:Antipyrine / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D003042:Cocaine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D003932:Heroin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D008691:Methadone / Q000493:pharmacokinetics*; D009294:Narcotics / Q000493:pharmacokinetics; D018384:Oxidative Stress / Q000187:drug effects; D010477:Perfusion; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002250:Carbon Radioisotopes; D009294:Narcotics; D014662:Vasoconstrictor Agents; D003932:Heroin; D003042:Cocaine; D000983:Antipyrine; D008691:Methadone