Maternal-Fetal Transfer of Cefazolin in the First Twenty Weeks of Pregnancy

Abstract

Maternal-fetal transfer of cefazolin was investigated with use of a single 14-mg/kg intramuscular dose administered to 40 gravidas before elective hysterectomy. The half-life of cefazolin in maternal serum was 1.5 hr with mean concentrations at 2 and 4 hr of 39 and 16 microgram/ml, respectively. By microbiological assay, cefazolin was not detected in brain, cerebrospinal fluid, lung, liver, or kidney of the fetus but was present in concentrations of 1-11 microgram/ml in 12 of 27 individual samples of fetal serum from 0.75 to 10.66 hr. Cefazolin appeared in fetal urine from 2.17 to 19.5 hr at levels of less than 5 microgram/ml with a half-life of 5.4 hr. Cefazolin was present in the amniotic fluid of fetuses older than 14 weeks in concentrations of less than 1 microgram/ml from 9 to 21.75 hr. After administration of a single dose to the mother early in pregnancy, the fetal distribution of cefazolin is limited to the body fluids.

Prediction of Maternal and Fetoplacental Concentrations of Cefazolin, Cefuroxime, and Amoxicillin during Pregnancy Using Bottom-Up Physiologically Based Pharmacokinetic Models

“…While the predicted transplacental diffusion verified with available maternal, umbilical, amniotic and placental data at term (Fig. 2a, 3a and 4), the availability of cefuroxime (Takase et al, 1979) and cefazolin (Bernard et al, 1977) data from different fetal organs allowed us to challenge the implemented model to simultaneously assess the integrity of dynamic physiology and drug properties for predicting fetal cefuroxime exposureat term (Fig. 2b) as well as cefazolin exposure at the end of first trimester (Fig.…”

“…See ''Methods'' section for trial settings. : 28-40 GWs (van Hasselt et al, 2014), Plot C: 19-33 GWs (Bernard et al, 1977), Plot D: 23-32 GWs (Brown et al, 1990), Plot E: 17-40 GWs (Allegaert et al, 2009), Plot F: 39…”

“…The drug is administered via intravenous or intramuscular routes. Different clinical studies have evaluated the pharmacokinetics of cefazolin during late pregnancy and have reported the concentrations in maternal circulation, the umbilical cord and amniotic fluid (Bernard et al, 1977;Philipson et al, 1987;Brown et al, 1990;Fiore Mitchell et al, 2001;Allegaert et al, 2009;Elkomy et al, 2014;van Hasselt et al, 2014;Grupper et al, 2017;Kram et al, 2017).…”

“…Trial design P9: Single intravenous bolus dose of either 2000 (or 3000) mg cefazolin (Kram et al, 2017); 20 trials of 65 pregnant women at 39 GWs and aged 27 -32 years. Conc reported at 1.833hr after dose administration Trial design P10: Single intramuscular dose of 14 mg/kg mg cefazolin (Bernard et al, 1977); 20 trials of 40 pregnant women between 15 -20 GWs and aged 18 -45 years.…”

Pharmacokinetics of Oral Cefatrizine in Pregnant and Non-Pregnant Women with Reference to Fetal Distribution

“…For low (20-40%) or moderately (50-60%) or highly (75-95%) bound antimicrobials like ampicillin [17][18][19] , cefuroxime [20] , piperacillin [11,21,22] , ceftazidime [23] and imipenem [24] , or penicillin V [10] , or cefazolin [25] and cefoxitin [23] , respectively, the net effect is usually the decrease of the antibiotic's plasma half-life. In some occasions, T 1/2 values have been reported to remain practically unchanged during pregnancy [10,19,22,24] .…”