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

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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.

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Acknowledgments

This work was supported by Department of Health and Human Services contract 223-03-8726 from the Office of Women’s Health, US FDA. All authors have no conflicts of interest that are directly relevant to the content of this study.

Author information

Author notes

  1. Jennifer Hardman

    Present address: Froedtert Hospital, Milwaukee, WI, USA

  2. Loraine Endres

    Present address: Department of Obstetrics and Gynecology, NorthShore University HealthSystem, Evanston, IL, USA

  3. Thomas M. Jenkins

    Present address: Legacy Medical Group, Maternal Fetal Medicine, Portland, OR, USA

  4. Sarah J. Kilpatrick

    Present address: Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Authors and Affiliations

  1. Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, 833 S Wood Street, Room 164, Chicago, IL, 60612, USA

    James H. Fischer, Jennifer Hardman, Hyunyoung Jeong, Kelly Deyo, Patricia A. Fischer & Keith A. Rodvold

  2. Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA

    Gloria E. Sarto & Thomas M. Jenkins

  3. Department of Obstetrics and Gynecology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA

    Loraine Endres, Sarah J. Kilpatrick & Stacie Geller

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  1. James H. Fischer
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Correspondence to James H. Fischer.

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Fischer, J.H., Sarto, G.E., Hardman, J. et al. Influence of Gestational Age and Body Weight on the Pharmacokinetics of Labetalol in Pregnancy. Clin Pharmacokinet 53, 373–383 (2014). https://doi.org/10.1007/s40262-013-0123-0

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