title: Population Pharmacokinetics of Cefazolin in Serum and Adipose Tissue From Overweight and Obese Women Undergoing Cesarean Delivery.
abstract: The optimal antibiotic prophylaxis dosing regimen of cefazolin for cesarean delivery (CD) in overweight and obese women is unknown. This study was done to compare the duration that cefazolin concentrations remain above the minimum inhibitory concentration (MIC) in adipose tissue (AT). Serum and AT concentrations from 3 previous studies in CD patients were comodeled using the nonparametric adaptive grid algorithm in Pmetrics. AT concentrations for 5000 overweight and obese patients receiving 1-, 2-, and 3-g cefazolin regimens were simulated to calculate the probability that free drug concentrations remained above an MIC of 2 μg/mL at 1, 1.5, and 2 hours after administration. Sixty-seven patients (mean body mass index 38.7 kg/m2; range 25.5-55.8 kg/m2) provided data. A 2-compartment model with 1 of the compartments representing AT fit the data best. Final model parameters were clearance 7.38 ± 5.34 L/h, volume of central compartment 11.8±9.36 L, and AT volume of distribution 80.12 ± 55.47 L. The mean±SD (median) penetration ratio of cefazolin into AT was 0.81 ± 2.06 (0.62). At 1.5 and 2 hours, 1-, 2-, and 3-g regimens achieved AT concentrations above the MIC in 71.2%, 92.4%, and 94.7%, and 55.7%, 86.8%, and 91.7%, respectively, of simulated patients. Cefazolin achieved good penetration into AT. Because CD duration is commonly less than 1.5 hours, a 2-g dose has a high probability of providing AT concentrations above the target pathogens' MIC for overweight and obese females. A second dose may be considered for longer surgeries.
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.
authors.forename: Mordechai
authors.initials: M
authors.lastname: Grupper
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kuti
authors.affiliation: Miller Children's and Women's Hospital, Long Beach, CA, USA.
authors.forename: Morgan L
authors.initials: ML
authors.lastname: Swank
authors.affiliation: University of South Florida, Tampa, FL, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Maggio
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, Women & Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Brenna L
authors.initials: BL
authors.lastname: Hughes
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019072:Antibiotic Prophylaxis; D002437:Cefazolin / Q000097:blood / Q000493:pharmacokinetics*; D002585:Cesarean Section; D005260:Female; D006801:Humans; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009010:Monte Carlo Method; D050177:Overweight / Q000097:blood / Q000378:metabolism*; D011247:Pregnancy; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D002437:Cefazolin
keywords: Monte Carlo simulation; obesity; pharmacokinetics; prophylaxis; surgery