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.
Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , Methadone/administration & dosage , Opioid-Related Disorders/rehabilitation , Oxidoreductases, N-Demethylating/genetics , Pregnancy Complications/drug therapy , Adolescent , Adult , Cytochrome P-450 CYP2B6 , Cytochrome P-450 CYP2C19 , Cytochrome P-450 CYP3A/genetics , Decision Making , Dose-Response Relationship, Drug , Female , Genotype , Half-Life , Humans , Longitudinal Studies , Opiate Substitution Treatment/methods , Peripartum Period , Polymorphism, Single Nucleotide , Pregnancy , Pregnancy Trimester, Third , Prospective Studies , Stereoisomerism , Young AdultABSTRACT
A case of peripheral primitive neuroectodermal tumor of the parotid gland region in a 38-yr-old woman is reported. She had a 1-yr history of a large, firm, and slightly tender left parotid-region mass. CT scan showed an invasive tumor involving the parotid gland, mandible, infratemporal fossa, and parapharyngeal space. Fine-needle aspiration cytology of the mass showed a highly cellular, poorly cohesive smear pattern exhibiting small cuboidal cells, with fibrillary cytoplasm forming occasional rosette-like structures. Numerous intact single cells with fragile cytoplasm, finely granular chromatin, and inconspicuous nucleoli were present together with free-lying nuclei in the background. Histologic, immunohistochemical, and ultrastructural findings confirmed the diagnosis. Diagn. Cytopathol. 2000;22:161-166. Published 2000 Wiley-Liss, Inc.