Clinical Pharmacokinetics

, Volume 53, Issue 4, pp 373–383

Influence of Gestational Age and Body Weight on the Pharmacokinetics of Labetalol in Pregnancy

  • James H. Fischer
  • Gloria E. Sarto
  • Jennifer Hardman
  • Loraine Endres
  • Thomas M. Jenkins
  • Sarah J. Kilpatrick
  • Hyunyoung Jeong
  • Stacie Geller
  • Kelly Deyo
  • Patricia A. Fischer
  • Keith A. Rodvold
Original Research Article

DOI: 10.1007/s40262-013-0123-0

Cite this article as:
Fischer, J.H., Sarto, G.E., Hardman, J. et al. Clin Pharmacokinet (2014) 53: 373. doi:10.1007/s40262-013-0123-0

Abstract

Background and Objectives

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.

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • James H. Fischer
    • 1
  • Gloria E. Sarto
    • 2
  • Jennifer Hardman
    • 1
    • 3
  • Loraine Endres
    • 4
    • 5
  • Thomas M. Jenkins
    • 2
    • 6
  • Sarah J. Kilpatrick
    • 4
    • 7
  • Hyunyoung Jeong
    • 1
  • Stacie Geller
    • 4
  • Kelly Deyo
    • 1
  • Patricia A. Fischer
    • 1
  • Keith A. Rodvold
    • 1
  1. 1.Department of Pharmacy Practice, College of PharmacyUniversity of Illinois at ChicagoChicagoUSA
  2. 2.Department of Obstetrics and Gynecology, School of Medicine and Public HealthUniversity of Wisconsin-MadisonMadisonUSA
  3. 3.Froedtert HospitalMilwaukeeUSA
  4. 4.Department of Obstetrics and Gynecology, College of MedicineUniversity of Illinois at ChicagoChicagoUSA
  5. 5.Department of Obstetrics and GynecologyNorthShore University HealthSystemEvanstonUSA
  6. 6.Legacy Medical Group, Maternal Fetal MedicinePortlandUSA
  7. 7.Department of Obstetrics and GynecologyCedars-Sinai Medical CenterLos AngelesUSA