Pharmacologic evidence to support clinical decision making for peripartum methadone treatment

D. L. Bogen*, J. M. Perel, J. C. Helsel, B. H. Hanusa, M. Romkes, T. Nukui, C. R. Friedman, K. L. Wisner

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)441-451
Number of pages11
JournalPsychopharmacology
Volume225
Issue number2
DOIs
StatePublished - Jan 1 2013

Keywords

  • CYP2B6
  • CYP2C19
  • CYP3A4
  • Half-life
  • Pharmacokinetics
  • Postpartum
  • Pregnancy
  • R-Methadone
  • Rac-methadone
  • S-Methadone

ASJC Scopus subject areas

  • Pharmacology

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