Document Detail


Pharmacologic evidence to support clinical decision making for peripartum methadone treatment.
MedLine Citation:
PMID:  22926004     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Limited pharmacological data are available to guide methadone treatment during pregnancy and postpartum.
OBJECTIVES: Study goals were to (1) characterize changes in methadone dose across childbearing, (2) determine enantiomer-specific methadone withdrawal kinetics from steady state during late pregnancy, (3) assess enantiomer-specific changes in methadone level/dose (L/D) ratios across childbearing, and (4) explore relationships between CYP2B6, CYP2C19, and CYP3A4 single-nucleotide polymorphisms and maternal dose, plasma concentration, and L/D.
METHODS: Methadone dose changes and timed plasma samples were obtained for women on methadone (n = 25) followed prospectively from third trimester of pregnancy to 3 months postpartum.
RESULTS: Participants were primarily white, Medicaid insured, and multiparous. All women increased their dose from first to end of second trimester (mean peak increase = 23 mg/day); 71 % of women increased from second trimester to delivery (mean peak increase = 19 mg/day). Half took a higher dose 3 months postpartum than at delivery despite significantly larger clearance during late pregnancy. Third trimester enantiomer-specific methadone half-lives (range R-methadone 14.7-24.9 h; S-methadone, 8.02-18.9 h) were about half of those reported in non-pregnant populations. In three women with weekly 24-h methadone levels after delivery, L/D increased within 1-2 weeks after delivery. Women with the CYP2B6 Q172 variant GT genotype have consistently higher L/D values for S-methadone across both pregnancy and postpartum.
CONCLUSIONS: Most women require increases in methadone dose across pregnancy. Given the shorter half-life and larger clearances during pregnancy, many pregnant women may benefit from split methadone dosing. L/D increases quickly after delivery and doses should be lowered rapidly after delivery.
Authors:
D L Bogen; J M Perel; J C Helsel; B H Hanusa; M Romkes; T Nukui; C R Friedman; K L Wisner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-25
Journal Detail:
Title:  Psychopharmacology     Volume:  225     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-04     Completed Date:  2013-06-10     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  441-51     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aryl Hydrocarbon Hydroxylases / genetics*
Cytochrome P-450 CYP3A / genetics
Decision Making
Dose-Response Relationship, Drug
Female
Genotype
Half-Life
Humans
Longitudinal Studies
Methadone / administration & dosage*
Opiate Substitution Treatment / methods
Opioid-Related Disorders / rehabilitation*
Oxidoreductases, N-Demethylating / genetics*
Peripartum Period
Polymorphism, Single Nucleotide
Pregnancy
Pregnancy Complications / drug therapy*
Pregnancy Trimester, Third
Prospective Studies
Stereoisomerism
Young Adult
Grant Support
ID/Acronym/Agency:
5MO1 RR00056/RR/NCRR NIH HHS; K12 HD043441/HD/NICHD NIH HHS; K12 HD043441/HD/NICHD NIH HHS; M01 RR000056/RR/NCRR NIH HHS; P30 CA047904/CA/NCI NIH HHS; P30CA047904/CA/NCI NIH HHS; R01 MH 075921/MH/NIMH NIH HHS; R01 MH075921/MH/NIMH NIH HHS; UL1 RR024153/RR/NCRR NIH HHS; UL1 RR024153/RR/NCRR NIH HHS; UL1 TR000005/TR/NCATS NIH HHS; UL1TR000005/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
EC 1.14.13.-/cytochrome P-450 CYP2B6; EC 1.14.13.67/CYP3A4 protein, human; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C19 protein, human; EC 1.14.14.1/Cytochrome P-450 CYP3A; EC 1.5.-/Oxidoreductases, N-Demethylating; UC6VBE7V1Z/Methadone
Comments/Corrections

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