Pharmacokinetics of prophylactic cefazolin in parturients undergoing cesarean delivery

Antimicrob Agents Chemother. 2014 Jun;58(6):3504-13. doi: 10.1128/AAC.02613-13. Epub 2014 Apr 14.

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. [corrected] 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.

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Antibiotic Prophylaxis*
  • Cefazolin / administration & dosage
  • Cefazolin / blood
  • Cefazolin / pharmacokinetics*
  • Cesarean Section / adverse effects
  • Female
  • Half-Life
  • Humans
  • Infant, Newborn
  • Pregnancy
  • Preoperative Care
  • Surgical Wound Infection / prevention & control*
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Cefazolin