title: Population pharmacokinetics of oseltamivir in non-pregnant and pregnant women.
abstract: OBJECTIVE
  Physiological changes in pregnancy are expected to alter the pharmacokinetics of various drugs. The objective of this study was to evaluate systematically the pharmacokinetics of oseltamivir (OS), a drug used in the treatment of influenza during pregnancy.
  
  
  METHODS
  A multicentre steady-state pharmacokinetic study of OS was performed in 35 non-pregnant and 29 pregnant women. Plasma concentration-time profiles were analyzed using both non-compartmental and population pharmacokinetic modelling (pop PK) and simulation approaches. A one compartment population pharmacokinetic model with first order absorption and elimination adequately described the pharmacokinetics of OS.
  
  
  RESULTS
  The systemic exposure of oseltamivir carboxylate (OC, active metabolite of OS) was reduced approximately 30 (19-36)% (P < 0.001) in pregnant women. Pregnancy significantly (P < 0.001) influenced the clearance (CL/F) and volume of distribution (V/F) of OC. Both non-compartmental and population pharmacokinetic approaches documented approximately 45 (23-62)% increase in clearance (CL/F) of OC during pregnancy.
  
  
  CONCLUSIONS
  Based on the decrease in exposure of the active metabolite, the currently recommended doses of OS may need to be increased modestly in pregnant women in order to achieve comparable exposure with that of non-pregnant women.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, PA.
authors.forename: Venkateswaran C
authors.initials: VC
authors.lastname: Pillai
authors.affiliation: Clinical Pharmacology, Genentech, Inc, CA.
authors.forename: Kelong
authors.initials: K
authors.lastname: Han
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Women's Hospital, University of Pittsburgh Medical Center, PA.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Beigi
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, TX.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hankins
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, TX.
authors.forename: Shannon
authors.initials: S
authors.lastname: Clark
authors.affiliation: Department of Pharmacy and Obstetrics & Gynecology, University of Washington, WA.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Hebert
authors.affiliation: Department of Pharmacy and Obstetrics & Gynecology, University of Washington, WA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Easterling
authors.affiliation: Obstetric and Pediatric Pharmacology and Therapeutics Branch, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, MD, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Zajicek
authors.affiliation: Obstetric and Pediatric Pharmacology and Therapeutics Branch, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, MD, USA.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Women's Hospital, University of Pittsburgh Medical Center, PA.
authors.forename: Steve N
authors.initials: SN
authors.lastname: Caritis
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, PA.
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataramanan
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D053139:Oseltamivir / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D011247:Pregnancy; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; C535162:oseltamivir carboxylate
keywords: oseltamivir; population pharmacokinetics; pregnancy