title: Pharmacokinetics of cefazolin prophylaxis in obese gravidae at time of cesarean delivery.
abstract: OBJECTIVE
  The objective of the study was to compare the pharmacokinetics of 2 g and 3 g doses of cefazolin when used for perioperative prophylaxis in obese gravidae undergoing cesarean delivery.
  
  
  METHODS
  We performed a double-blinded, randomized controlled trial from August 2013 to April 2014. Twenty-six obese women were randomized to receive either 2 or 3 g intravenous cefazolin within 30 minutes of a skin incision. Serial maternal plasma samples were obtained at specific time points up to 8 hours after drug administration. Umbilical cord blood was obtained after placental delivery. Maternal adipose samples were obtained prior to fascial entry, after closure of the hysterotomy, and subsequent to fascial closure. Pharmacokinetic parameters were determined via noncompartmental analysis.
  
  
  RESULTS
  The median area under the plasma concentration vs time curve was significantly greater in the 3 g group than in the 2 g group (27204 μg/mL per minute vs 14058 μg/mL per minute; P = .001). Maternal plasma concentrations had an impact by body mass index. For every 1 kg/m(2) increase in body mass index at the time of the cesarean delivery, there was an associated 13.77 μg/mL lower plasma concentration of cefazolin across all time points (P = .01). By the completion of cesarean delivery, cefazolin concentrations in maternal adipose were consistently above the minimal inhibitory concentration for both Gram-positive and Gram-negative bacteria with both the 2 g and 3 g doses. The median umbilical cord blood concentrations were significantly higher in the 3 g vs the 2 g group (34.5 μg/mL and 21.4 μg/mL; P = .003).
  
  
  CONCLUSIONS
  Cefazolin concentrations in maternal adipose both at time of hysterotomy closure and fascial closure were above the minimal inhibitory concentration for both Gram-positive and Gram-negative bacteria when either 2 g or 3 g cefazolin was administered as perioperative surgical prophylaxis. Maternal cefazolin concentrations in plasma and maternal adipose tissue are related to both dose and body mass index.
authors.affiliation: Division of Maternal-Fetal Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO. Electronic address: youngom@upmc.edu.
authors.forename: Omar M
authors.initials: OM
authors.lastname: Young
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Imam H
authors.initials: IH
authors.lastname: Shaik
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Roxanna
authors.initials: R
authors.lastname: Twedt
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Anna
authors.initials: A
authors.lastname: Binstock
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA; Magee-Womens Research Institute, Pittsburgh, PA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Althouse
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA; Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA; Magee-Womens Research Institute, Pittsburgh, PA.
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataramanan
authors.affiliation: Division of Maternal-Fetal Medicine, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA; Magee-Womens Research Institute, Pittsburgh, PA.
authors.forename: Hyagriv N
authors.initials: HN
authors.lastname: Simhan
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA; Magee-Womens Research Institute, Pittsburgh, PA.
authors.forename: Harold C
authors.initials: HC
authors.lastname: Wiesenfeld
authors.affiliation: Division of Maternal-Fetal Medicine, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA; Magee-Womens Research Institute, Pittsburgh, PA.
authors.forename: Steve N
authors.initials: SN
authors.lastname: Caritis
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019072:Antibiotic Prophylaxis; D019540:Area Under Curve; D015992:Body Mass Index; D002437:Cefazolin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002585:Cesarean Section / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D016014:Linear Models; D008826:Microbial Sensitivity Tests; D009765:Obesity / Q000097:blood*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood*; D050151:Subcutaneous Fat / Q000737:chemistry*; D013530:Surgical Wound Infection / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D002437:Cefazolin
keywords: cefazolin; cesarean delivery; obesity; pharmacokinetics; surgical prophylaxis