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01-04-2014 | Original Research Article

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

Authors: 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

Published in: Clinical Pharmacokinetics | Issue 4/2014

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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Title: Influence of Gestational Age and Body Weight on the Pharmacokinetics of Labetalol in Pregnancy
Authors: 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
Publication date: 01-04-2014
Publisher: Springer International Publishing
Published in: Clinical Pharmacokinetics / Issue 4/2014
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-013-0123-0

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Springer Medicine

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

Abstract

Background and Objectives

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and Objectives

Methods

Results

Conclusions

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