title: Pharmacokinetics of sertraline across pregnancy and postpartum.
abstract: Insufficient data inform dosing of antidepressants and clinical monitoring for major depressive disorder (MDD) during the perinatal period. The objectives were to assess the pharmacokinetics of sertraline (SER) across pregnancy and postpartum. Participants treated with SER for MDD underwent serial sampling to measure steady-state concentrations of SER and norsertraline during the second and third trimesters and postpartum (total of 3 assessments). Blood was drawn before observed SER administration and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration. A sensitive high-performance liquid chromatography/mass spectrometric method for simultaneous determination of serum concentrations of SER and norsertraline was developed and validated. For each sampling period for SER, area under the serum concentration versus time curve, maximal serum concentration (Cmax), and the time at which Cmax occurred (Tmax) were determined. Of 11 women initially enrolled, 6 completed second- and third-trimester assessments, and 3 completed all 3 assessments (including the postpartum assessment). Mean changes on all pharmacokinetic parameters were nonsignificant between assessments, although there was a marked heterogeneity among individuals. Results were not significantly altered by incorporation of body weights into the analyses. The range of pharmacokinetic changes between individuals was broad, indicating heterogeneity regarding the impact of pregnancy on SER metabolism. Overall, lowest observed SER area under the curve and Cmax occurred in the third trimester (observed in 5 of 6 participants). Despite nonsignificant mean pharmacokinetic changes, the range of pharmacokinetic changes across pregnancy warrants careful monitoring of depressive symptoms in women with MDD in late pregnancy and further study.
authors.affiliation: Department of Psychiatry, Women's Mental Health Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. mfreeman@partners.org
authors.forename: Marlene P
authors.initials: MP
authors.lastname: Freeman
authors.forename: Paul E
authors.initials: PE
authors.lastname: Nolan
authors.forename: Melinda F
authors.initials: MF
authors.lastname: Davis
authors.forename: Marietta
authors.initials: M
authors.lastname: Anthony
authors.forename: Karen
authors.initials: K
authors.lastname: Fried
authors.forename: Martha
authors.initials: M
authors.lastname: Fankhauser
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Woosley
authors.forename: Francisco
authors.initials: F
authors.lastname: Moreno
mesh_terms: D015057:1-Naphthylamine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000328:Adult; D001835:Body Weight; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D049590:Postpartum Period / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000378:metabolism; D011262:Pregnancy Trimester, Second / Q000378:metabolism*; D011263:Pregnancy Trimester, Third / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020280:Sertraline / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D015057:1-Naphthylamine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C065162:desmethylsertraline