Cefazolin pharmacokinetics in maternal plasma and amniotic fluid during pregnancy

Karel Allegaert*, Tim van Mieghem, Rene Verbesselt, Jan de Hoon, Maissa Rayyan, Roland Devlieger, Jan Deprest, Brian J. Anderson

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

43 Citations (Scopus)

Abstract

Objective: To study cefazolin pharmacokinetics in maternal plasma and amniotic fluid during pregnancy. Study Design: Newly collected time-concentrations profiles and reported studies investigating cefazolin disposition (plasma, amniotic fluid) were pooled. Nonlinear mixed effect modeling was applied. A 2-compartment linear disposition model was used to fit cefazolin plasma observations. A third compartment was used to model amniotic fluid concentration. Results: One hundred eighty-seven plasma and 96 amniotic fluid samples were collected in 82 pregnancies (17-40 weeks gestational age). Cefazolin clearance and distribution estimates were 7.44 L/h and 12.04 L without gestational age-dependent trends in maternal plasma. The equilibration half-life (Teq) between plasma and amniotic fluid at term gestational age was 4.4 hours, increased with decreasing gestational age, and was 9.09 times longer in patients with polyhydramnios. Conclusion: Cefazolin clearance and distribution volume are increased during pregnancy. The cefazolin Teq depends on gestational age and polyhydramnios. On the basis of these observations, dosing regimes to attain higher amniotic fluid concentrations were formulated.

Original languageEnglish
Pages (from-to)170.e1-170.e7
JournalAmerican Journal of Obstetrics and Gynecology
Volume200
Issue number2
DOIs
Publication statusPublished - Feb 2008
Externally publishedYes

Bibliographical note

Funding Information:
Drs Allegaert and Deprest are supported by the Fonds Wetenschappelijk Onderzoek-Vlaanderen. Dr Devlieger is supported by the Clinical Research Fund of the University Hospitals, Leuven. Dr van Mieghem is supported by a Grant of the EC (EuroSTEC, LSHC-CT-2006-037409).

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