title: Pharmacokinetics of oseltamivir among pregnant and nonpregnant women.
abstract: We sought to delineate the pharmacokinetics (PK) of oseltamivir and its active metabolite oseltamivir carboxylate during pregnancy. Physiologic changes of pregnancy, including increased renal filtration and secretion, may increase the clearance of oseltamivir carboxylate. Sixteen pregnant women taking oseltamivir for prophylaxis or treatment of suspected/proven influenza infection were enrolled. Twenty-three nonpregnant reproductive-age females served as the control group. The primary PK endpoint was area under the plasma concentration time curve for oseltamivir carboxylate. Pregnancy did not alter the PK parameters of the parent compound, oseltamivir. However, for oseltamivir carboxylate the area under the plasma concentration time curve was significantly lower (P = .007) and the apparent clearance significantly higher (P = .006) in pregnant women compared with nonpregnant women. Pregnancy produces lower systemic levels of oseltamivir carboxylate. Increasing the dose and/or dosing frequency of oseltamivir during pregnancy may be necessary to achieve comparable exposure in pregnant and nonpregnant women.
authors.affiliation: Division of Reproductive Infectious Diseases, Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Women's Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Beigi
authors.forename: Kelong
authors.initials: K
authors.lastname: Han
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataramanan
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hankins
authors.forename: Shannon
authors.initials: S
authors.lastname: Clark
authors.forename: Mary F
authors.initials: MF
authors.lastname: Hebert
authors.forename: Thomas
authors.initials: T
authors.lastname: Easterling
authors.forename: Anne
authors.initials: A
authors.lastname: Zajicek
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Ren
authors.forename: Donald R
authors.initials: DR
authors.lastname: Mattison
authors.forename: Steve N
authors.initials: SN
authors.lastname: Caritis
mesh_terms: D000293:Adolescent; D000328:Adult; D019072:Antibiotic Prophylaxis; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007251:Influenza, Human / Q000097:blood / Q000188:drug therapy*; D008657:Metabolic Clearance Rate; D053139:Oseltamivir / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011247:Pregnancy / Q000097:blood / Q000502:physiology*; D011251:Pregnancy Complications, Infectious / Q000097:blood / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; C535162:oseltamivir carboxylate