title: Ondansetron Exposure Changes in a Pregnant Woman.
abstract: Pregnancy results in many physiologic changes that can alter the pharmacokinetic profiles of medications used during pregnancy. One of the primary factors leading to these pharmacokinetic changes is altered activity of drug-metabolizing enzymes. Ondansetron is a substrate of cytochrome P450 (CYP) 3A4 (primary metabolic pathway), 2D6, and 1A2, all of which are altered during pregnancy. We evaluated the pharmacokinetics of ondansetron at three different gestational time points in a 26-year-old, pregnant, Caucasian woman with normal liver and kidney function, who was maintained on ondansetron 8 mg administered orally 3 times/day throughout her pregnancy. Serial plasma samples were collected from the subject over one 8-hour dosing interval at 14, 24, and 35 weeks' gestation (representing early-, mid-, and late-pregnancy time points, respectively). Ondansetron plasma concentrations were determined using liquid chromatography-tandem mass spectrometry. Ondansetron area under the plasma concentration-time curve decreased progressively across gestation (634 ng hr/ml in early pregnancy, 553 ng hr/ml in mid-pregnancy, and 387 ng hr/ml in late pregnancy), with a corresponding increase in apparent oral clearance (12.6 L/hr in early-pregnancy, 14.5 L/hr in mid-pregnancy, and 20.7 L/hr in late-pregnancy). The decreased area under the plasma concentration-time curve and exposure to ondansetron across gestation is likely due to increased activity of CYP3A4 and CYP2D6 during pregnancy. We were not able to study this patient during the postpartum period; however, as with other CYP3A4 and CYP2D6 substrates, the apparent activities of these isoenzymes are likely return to baseline. To our knowledge, this is the first report to describe ondansetron pharmacokinetics across gestation. Additional pharmacokinetic and pharmacodynamic data are needed to confirm our results and to evaluate clinical impact; however, in the meantime, clinicians should be aware of these pharmacokinetic changes in ondansetron exposure during pregnancy.
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.|Department of Pharmaceutical Science, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Lara S
authors.initials: LS
authors.lastname: Lemon
authors.affiliation: Department of Pharmaceutical Science, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Departments of Pharmacy and Obstetrics, and Gynecology, University of Washington, Seattle, Washington.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Hebert
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hankins
authors.affiliation: Department of Obstetrics and Gynecology Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: David M
authors.initials: DM
authors.lastname: Haas
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Steve N
authors.initials: SN
authors.lastname: Caritis
authors.affiliation: Department of Pharmaceutical Science, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania. rv@pitt.edu.|Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania. rv@pitt.edu.
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataramanan
mesh_terms: D000328:Adult; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D005260:Female; D006801:Humans; D017294:Ondansetron / Q000493:pharmacokinetics*; D011247:Pregnancy / Q000378:metabolism*
chemical_list: D017294:Ondansetron; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
keywords: ondansetron; pharmacokinetics; pregnancy