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

Publication ,  Journal Article
Grupper, M; Kuti, JL; Swank, ML; Maggio, L; Hughes, BL; Nicolau, DP
Published in: J Clin Pharmacol
June 2017

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.

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Published In

J Clin Pharmacol

DOI

EISSN

1552-4604

Publication Date

June 2017

Volume

57

Issue

6

Start / End Page

712 / 719

Location

England

Related Subject Headings

  • Young Adult
  • Pregnancy
  • Pharmacology & Pharmacy
  • Overweight
  • Monte Carlo Method
  • Models, Biological
  • Microbial Sensitivity Tests
  • Humans
  • Female
  • Cesarean Section
 

Citation

APA
Chicago
ICMJE
MLA
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Grupper, M., Kuti, J. L., Swank, M. L., Maggio, L., Hughes, B. L., & Nicolau, D. P. (2017). Population Pharmacokinetics of Cefazolin in Serum and Adipose Tissue From Overweight and Obese Women Undergoing Cesarean Delivery. J Clin Pharmacol, 57(6), 712–719. https://doi.org/10.1002/jcph.851
Grupper, Mordechai, Joseph L. Kuti, Morgan L. Swank, Lindsay Maggio, Brenna L. Hughes, and David P. Nicolau. “Population Pharmacokinetics of Cefazolin in Serum and Adipose Tissue From Overweight and Obese Women Undergoing Cesarean Delivery.J Clin Pharmacol 57, no. 6 (June 2017): 712–19. https://doi.org/10.1002/jcph.851.
Grupper M, Kuti JL, Swank ML, Maggio L, Hughes BL, Nicolau DP. Population Pharmacokinetics of Cefazolin in Serum and Adipose Tissue From Overweight and Obese Women Undergoing Cesarean Delivery. J Clin Pharmacol. 2017 Jun;57(6):712–9.
Grupper, Mordechai, et al. “Population Pharmacokinetics of Cefazolin in Serum and Adipose Tissue From Overweight and Obese Women Undergoing Cesarean Delivery.J Clin Pharmacol, vol. 57, no. 6, June 2017, pp. 712–19. Pubmed, doi:10.1002/jcph.851.
Grupper M, Kuti JL, Swank ML, Maggio L, Hughes BL, Nicolau DP. Population Pharmacokinetics of Cefazolin in Serum and Adipose Tissue From Overweight and Obese Women Undergoing Cesarean Delivery. J Clin Pharmacol. 2017 Jun;57(6):712–719.

Published In

J Clin Pharmacol

DOI

EISSN

1552-4604

Publication Date

June 2017

Volume

57

Issue

6

Start / End Page

712 / 719

Location

England

Related Subject Headings

  • Young Adult
  • Pregnancy
  • Pharmacology & Pharmacy
  • Overweight
  • Monte Carlo Method
  • Models, Biological
  • Microbial Sensitivity Tests
  • Humans
  • Female
  • Cesarean Section