Am J Perinatol 2006; 23(5): 287-294
DOI: 10.1055/s-2006-947160
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Methadone Metabolism by Early Gestational Age Placentas

Todd Lewis Hieronymus1 , Tatiana N. Nanovskaya2 , Sujal V. Deshmukh3 , Ricardo Vargas1 , Gary D.V Hankins1 , Mahmoud S. Ahmed1 , 2
  • 1Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas
  • 2Department of Obstetrics & Gynecology, University of Texas Medical Branch, Galveston, Texas
  • 3Merck & Co., Inc., Boston, Massachusetts
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Publikationsdatum:
23. Juni 2006 (online)

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ABSTRACT

The objective of this study was to identify the enzyme that metabolizes methadone in preterm placentas. Microsomal fractions were obtained from preterm (17 to 34 weeks) placentas (36 total; 12 per each gestational age group) and their activity in metabolizing methadone to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) was determined. The enzyme catalyzing the reaction was identified by using chemical inhibitors selective for various cytochrome P450 isozymes and monoclonal antibodies raised against them. The metabolism of methadone by microsomes revealed saturation kinetics. Methadone was N-demethylated to EDDP by aromatase. The affinity of methadone to aromatase (apparent K m) did not change with gestation, but the activity of the enzyme (V max) increased and varied widely between individual placentas. Aromatase/CYP19 is the placental enzyme metabolizing methadone during pregnancy. The variability in enzyme activity among individuals should be reflected by the concentration of methadone in the fetal circulation and might be one of the factors affecting the incidence and intensity of neonatal abstinence syndrome.

REFERENCES

Mahmoud S AhmedPh.D. 

Departments of Obstetrics & Gynecology and Pharmacology & Toxicology, University of Texas Medical Branch

301 University Blvd., Galveston, TX