title: Influence of gestational age and body weight on the pharmacokinetics of labetalol in pregnancy.
abstract: OBJECTIVE
  Labetalol is frequently prescribed for the treatment of hypertension during pregnancy; however, the influence of pregnancy on labetalol pharmacokinetics is uncertain, with inconsistent findings reported by previous studies. This study examined the population pharmacokinetics of oral labetalol during and after pregnancy in women receiving labetalol for hypertension.
  
  
  METHODS
  Data were collected from 57 women receiving the drug for hypertension from the 12th week of pregnancy through 12 weeks postpartum using a prospective, longitudinal design. A sparse sampling strategy guided collection of plasma samples. Samples were assayed for labetalol by high-performance liquid chromatography. Estimation of population pharmacokinetic parameters and covariate effects was performed by nonlinear mixed effects modeling using NONMEM. The final population model was validated by bootstrap analysis and visual predictive check. Simulations were performed with the final model to evaluate the appropriate body weight to guide labetalol dosing.
  
  
  RESULTS
  Lean body weight (LBW) and gestational age, i.e. weeks of pregnancy, were identified as significantly influencing oral clearance (CL/F) of labetalol, with CL/F ranging from 1.4-fold greater than postpartum values at 12 weeks' gestational age to 1.6-fold greater at 40 weeks. Doses adjusted for LBW provide more consistent drug exposure than doses adjusted for total body weight. The apparent volumes of distribution for the central compartment and at steady-state were 1.9-fold higher during pregnancy.
  
  
  CONCLUSIONS
  Gestational age and LBW impact the pharmacokinetics of labetalol during pregnancy and have clinical implications for adjusting labetalol doses in these women.
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, 833 S Wood Street, Room 164, Chicago, IL, 60612, USA, jfischer@uic.edu.
authors.forename: James H
authors.initials: JH
authors.lastname: Fischer
authors.forename: Gloria E
authors.initials: GE
authors.lastname: Sarto
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hardman
authors.forename: Loraine
authors.initials: L
authors.lastname: Endres
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Jenkins
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Kilpatrick
authors.forename: Hyunyoung
authors.initials: H
authors.lastname: Jeong
authors.forename: Stacie
authors.initials: S
authors.lastname: Geller
authors.forename: Kelly
authors.initials: K
authors.lastname: Deyo
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Fischer
authors.forename: Keith A
authors.initials: KA
authors.lastname: Rodvold
mesh_terms: D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001835:Body Weight / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy; D007741:Labetalol / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008137:Longitudinal Studies; D011247:Pregnancy; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D007741:Labetalol