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To quantify cefazolin exposure in plasma and subcutaneous adipose tissue during abdominal surgery, and to build a popPK model comparing standard anthropometrics, calculated body-composition metrics, and directly measured body-composition values as predictors of interindividual variability. A single center prospective study was conducted at Robert Wood Johnson Barnabas University Hospital, NJ, USA. Institutional standard for dosing was 2 g &lt; 120 kg, or 3 g of cefazolin for subjects \u2265 120 kg for 101 adult subjects. Serial blood samples and subcutaneous adipose tissue samples were collected for the assessment of cefazolin concentration. All subjects received body composition assessments. Cefazolin concentrations in plasma remained within the therapeutic range in all stratification groups, yet subcutaneous adipose tissue concentrations failed to meet therapeutic cut offs, with 2- to 8.5-fold decrease in target attainment in subjects with increasing body fat percentages and BMI. A three-compartment biophase model best characterized our data and served as our base popPK model. Stepwise covariate modeling of measured body composition metrics outperformed both calculated body composition metrics and standard anthropomorphic values. The results support the claim that existing weight-based dosing methods fall short at the site of action, while simultaneously providing a proof of concept for the first in-human body composition informed popPK model. Measured body composition metrics can enhance characterization of cefazolin prophylactic exposure for subjects with obesity receiving abdominal surgery.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01677-25","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T14:12:46Z","timestamp":1780063966000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Cefazolin surgical prophylaxis in obesity: a body composition-driven population pharmacokinetic approach"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0655-8480","authenticated-orcid":true,"given":"Andrew","family":"Wassef","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey","place":["Piscataway, 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