Article Text

AMNIOTIC FLUID CEFAZOLIN EQUILIBRATION HALF LIFE REFLECTS MATURATION OF FETAL RENAL DRUG CLEARANCE
  1. K Allegaert1,
  2. R Devlieger1,
  3. L Lewi1,
  4. R Verbesselt2,
  5. M Rayyan1,
  6. J deHoon2,
  7. A Debeer1,
  8. G Naulaers1
  1. 1Division of Woman and Child, University Hospitals Leuven, Leuven, Belgium
  2. 2Center for Clinical Pharmacology, University Hospitals Leuven, Leuven, Belgium

Abstract

Introduction Renal drug clearance matures in a postmenstrual age (PMA)-dependent sigmoidal trend.1 It is therefore anticipated that maturation of fetal renal drug clearance also depends on PMA. Cefazolin is administered during in utero surgery, but data on amniotic fluid (AF) disposition are limited. Such observations likely reflect fetal renal drug handling.

Methods Newly collected and reported studies on cefazolin disposition (plasma, AF) were pooled. Non-linear mixed effect modelling was applied. A two-compartment linear disposition model was used to fit maternal cefazolin plasma, a third compartment to model AF.

Results Data were available in 82 pregnancies (17–40 weeks). Estimated cefazolin clearance in maternal plasma was 7.44 L/h. A GA-dependent trend in clearance was not observed. Equilibration half life (Teq) between maternal plasma and AF at term was 4.4 h, increased with decreasing GA, and was 9.09 times longer in cases with polyhydramnios.

Conclusions Fetal renal elimination clearance of cefazolin increases with GA, reflecting perinatal maturation of renal clearance. The longer Teq with polyhydramnios reflects a higher distribution volume.

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