title: Carbamazepine clearance and seizure stability during pregnancy.
abstract: The aims of this study were to characterize the alterations in total and free carbamazepine (CBZ) and in total and free carbamazepine-epoxide (CBZ-EPO) clearances during pregnancy, to calculate the change in free fractions of CBZ and CBZ-EPO during pregnancy, and to determine whether seizure worsening is associated with a low ratio to nonpregnant baseline concentration of total or free CBZ or CBZ-EPO. Women on CBZ were enrolled before conception or during pregnancy in this prospective, observational study. Concomitant medications and seizure frequency were recorded. Serum total and free CBZ and CBZ-EPO were collected at each visit. Changes in the clearance of all four compounds and free fractions of CBZ and CBZ-EPO were compared with nonpregnant baseline. During pregnancy, the ratios to baseline concentrations of total and free CBZ and CBZ-EPO were compared for months with and without increased seizure frequency. Total and free CBZ and CBZ-EPO clearances were calculated in 15 pregnancies in 12 women. Clearances did not change for any of these compounds during pregnancy. The free fraction of CBZ increased from 0.23 at baseline to a maximum of 0.32 in the third trimester (p=0.008). In the six women on CBZ monotherapy with adequate seizure diaries and blood sampling, seizure worsening did not correspond to a ratio to baseline concentration of less than 0.65 for total or free CBZ or CBZ-EPO. In conclusion, total and free CBZ and CBZ-EPO clearances did not change substantially during pregnancy, and seizure frequency worsening was not associated with decreased concentrations of total or free CBZ; therefore, therapeutic drug monitoring may not be necessary for all women on CBZ during pregnancy. Further studies with larger sample sizes are needed before definitive recommendations can be made. Carbamazepine monotherapy may be a relatively safe and cost effective treatment option for women with focal epilepsy syndromes during pregnancy.
authors.affiliation: Department of Neurology, and Division of Women's Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Johnson
authors.affiliation: Departments of Psychiatry, Pediatrics, and Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Zachary N
authors.initials: ZN
authors.lastname: Stowe
authors.affiliation: Departments of Psychiatry and Behavioral Sciences and Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Ritchie
authors.affiliation: Departments of Psychiatry and Behavioral Health, and Obstetrics and Gynecology The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: D Jeffrey
authors.initials: DJ
authors.lastname: Newport
authors.affiliation: Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Melanee L
authors.initials: ML
authors.lastname: Newman
authors.affiliation: Departments of Psychiatry, Pediatrics, and Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Bettina
authors.initials: B
authors.lastname: Knight
authors.affiliation: Department of Neurology, and Division of Women's Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: ppennell@partners.org.
authors.forename: Page B
authors.initials: PB
authors.lastname: Pennell
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002220:Carbamazepine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011446:Prospective Studies
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine
keywords: Carbamazepine; Clearance; Epilepsy; Free carbamazepine; Pregnancy; Seizure