Methadone metabolism in placentas from preterm pregnancies
| dc.contributor.advisor | Dr. Mahmoud Ahmed | en_US |
| dc.contributor.committeeMember | Dr. Joel Gallagher | en_US |
| dc.contributor.committeeMember | Dr. Gary Hankins | en_US |
| dc.creator | Todd Lewis Hieronymus | en_US |
| dc.date.accessioned | 2011-12-20T16:05:43Z | |
| dc.date.available | 2010-09-28 | en_US |
| dc.date.available | 2011-12-20T16:05:43Z | |
| dc.date.created | 2005-12-13 | en_US |
| dc.date.issued | 2005-07-20 | en_US |
| dc.description.abstract | The aim of this investigation is to identify and characterize the enzyme system responsible for the N-demethylation of methadone in human preterm placentas. The metabolism of methadone revealed typical Michaelis-Menten saturation kinetics. Methadone was N-demethylated to EDDP, only, by human placental aromatase. This was confirmed through the use of chemical inhibitors and monoclonal antibodies raised against specific CYP isoforms. The affinity of methadone to CYP19 remained relatively unchanged throughout gestation. However, the activity of the enzyme increased as gestation progressed, but showed wide variations between individual placentas. Taken together, it was shown that aromatase is the major enzyme responsible for the biotransformation of methadone throughout pregnancy. The variability in activity should affect the concentration of the drug within the fetal circulation. Accordingly, this might be an important factor affecting the occurrence and intensity of neonatal abstinence syndrome. | en_US |
| dc.format.medium | electronic | en_US |
| dc.identifier.other | etd-12132005-162423 | en_US |
| dc.identifier.uri | http://hdl.handle.net/2152.3/292 | |
| dc.language.iso | eng | en_US |
| dc.rights | Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works. | en_US |
| dc.subject | pregnancy | en_US |
| dc.subject | methadone maintenance programs | en_US |
| dc.subject | human placental aromatase/CYP19 | en_US |
| dc.title | Methadone metabolism in placentas from preterm pregnancies | en_US |
| dc.type.genre | thesis | en_US |
| dc.type.material | text | en_US |
| thesis.degree.department | Pharmacology and Toxicology | en_US |
| thesis.degree.grantor | The University of Texas Medical Branch | en_US |
| thesis.degree.level | Master | en_US |
| thesis.degree.name | Master of Science | en_US |