Pharmacokinetics of Prophylactic Cefazolin in Parturients Undergoing Cesarean Delivery

Abstract

The objectives of this work were (i) to characterize the pharmacokinetics of cefazolin in pregnant women undergoing elective cesarean delivery and in their neonates; (ii) to assess cefazolin transplacental transmission; (iii) to evaluate the dosing and timing of preoperative, prophylactic administration of cefazolin to pregnant women; and (iv) to investigate the impact of maternal dosing on therapeutic duration and exposure in newborns. Twenty women received 1 g of cefazolin preoperatively. Plasma concentrations of total cefazolin were analyzed from maternal blood samples taken before, during, and after delivery; umbilical cord blood samples obtained at delivery; and neonatal blood samples collected 24 h after birth. The distribution volume of cefazolin was 9.44 liters/h. The values for pre-and postdelivery clearance were 7.18 and 4.12 liters/h, respectively. Computer simulations revealed that the probability of maintaining free cefazolin concentrations in plasma above 8 mg/liter during scheduled caesarean surgery was <50% in the cord blood when cefazolin was administered in doses of <2 g or when it was administered <1 h before delivery. Therapeutic concentrations of cefazolin persisted in neonates >5 h after birth. Cefazolin clearance increases during pregnancy, and larger doses are recommended for surgical prophylaxis in pregnant women to obtain the same antibacterial effect as in nonpregnant patients. Cefazolin has a longer half-life in neonates than in adults. Maternal administration of up to 2 g of cefazolin is effective and produces exposure within clinically approved limits in neonates.

Population Pharmacokinetics of Cefazolin in Serum and Adipose Tissue From Overweight and Obese Women Undergoing Cesarean Delivery

“…The estimated clearance in the current study was 7.38 ± 5.34 L/h, which is similar to the estimates from a recent pharmacokinetic study 15 of obese (BMI ࣙ 30 kg/m 2 ) patients undergoing CD (8.4 ± 0.6 and 6.6 ± 0.6 L/h for 2 different dosing regimens). Our observed clearance was also similar to estimates from several pharmacokinetic studies conducted in pregnant patients not undergoing CD (7.44 ± 0.32 L/h, 23 7.18 ± 0.56 L/h, 24 and 7.3 ± 3 L/h 25 ). Increased cefazolin clearance in pregnancy, as compared with that of healthy nonpregnant young women (4.66 ± 0.74 L/h) 25 has been mainly attributed to increasing glomerular filtration rates during pregnancy because cefazolin is exclusively eliminated by this route.…”

“…The range of clearance estimate values in the current study was wider than those in other studies. This may be due to lack of sampling beyond 2 hours, differences in the method of estimation, restriction to overweight population in the current study, or the effects of anesthesia and surgical procedure …”

“…This may be due to lack of sampling beyond 2 hours, differences in the method of estimation, restriction to overweight population in the current study, or the effects of anesthesia and surgical procedure. [23][24][25][26] To the best of our knowledge, the current study is the first to simulate AT concentrations of cefazolin among overweight and obese pregnant patients for the purpose of guiding optimal dosage selection in this population. The mean ± SD and median penetration ratios were 0.81 ± 2.06 and 0.67, respectively.…”

Group B Streptococcus circumvents neutrophils and neutrophil extracellular traps during amniotic cavity invasion and preterm labor

“…For example, the use of human placental membranes ex vivo does not permit investigation of host immune cells, which may be recruited to prevent microbial invasion of the amniotic fluid and fetus during pregnancy. Also, as antibiotics are routinely administered during Cesarean sections (14–16), the transfer of these antibiotics to the human placenta can impose limitations on bacterial studies performed with placental membranes ex vivo. Although animal models of pregnancy address the role of host immune defenses during an active infection, lower mammalian models differ significantly from human pregnancy in key respects including dissimilarities in reproductive anatomy, placentation, mechanism of labor onset and sensitivity to pathogens.…”

Quantification of three beta‐lactam antibiotics in breast milk and human plasma by hydrophilic interaction liquid chromatography/positive‐ion electrospray ionization mass spectrometry

“…[5] Information on drug transfer into breast milk is essential to protect the infant from undesirable adverse effects of maternal consumption of drugs and to allow effective pharmacological treatment of breastfeeding mothers. [10][11][12][13] However, cephalosporins can modify the bowel flora and alter the gut defence mechanisms of the nursing infants, causing diarrhoea and malabsorption of nutrients. These drugs are the most frequently prescribed antibiotics and their use is regulated due to their possible adverse effects on human health, such as resistance development and allergic reactions.…”