Perioperative administration of cefazolin and metronidazole in obese and non-obese patients: a pharmacokinetic study in plasma and interstitial fluid

Dorn, Christoph and Petroff, David and Stoelzel, Melanie and Kees, Martin G. and Kratzer, Alexander and Dietrich, Arne and Kloft, Charlotte and Zeitlinger, Markus and Kees, Frieder and Wrigge, Hermann and Simon, Philipp (2021) Perioperative administration of cefazolin and metronidazole in obese and non-obese patients: a pharmacokinetic study in plasma and interstitial fluid. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 76 (8). pp. 2114-2120. ISSN 0305-7453, 1460-2091

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Abstract

Objectives: To assess plasma and tissue pharmacokinetics of cefazolin and metronidazole in obese patients undergoing bariatric surgery and non-obese patients undergoing intra-abdominal surgery. Patients and methods: Fifteen obese and 15 non-obese patients received an IV short infusion of 2g cefazolin and 0.5g metronidazole for perioperative prophylaxis. Plasma and microdialysate from subcutaneous tissue were sampled until 8h after dosing. Drug concentrations were determined by HPLC-UV. Pharmacokinetic parameters were calculated non-compartmentally. Results: In obese patients (BMI 39.5-69.3kg/m(2)) compared with non-obese patients (BMI 18.7-29.8kg/m(2)), mean C-max of total cefazolin in plasma was lower (115 versus 174mg/L) and V-ss was higher (19.4 versus 14.2L). The mean differences in t(1/2) (2.7 versus 2.4h), CL (5.14 versus 4.63L/h) and AUC(infinity) (402 versus 450mg.h/L) were not significant. The influence of obesity on the pharmacokinetics of metronidazole was similar (C-max 8.99 versus 14.7mg/L, V-ss 73.9 versus 51.8L, t(1/2) 11.9 versus 9.1h, CL 4.62 versus 4.13L/h, AUC(infinity) 116 versus 127mg.h/L). Regarding interstitial fluid (ISF), mean concentrations of cefazolin remained >4mg/L until 6h in both groups, and those of metronidazole up to 8h in the non-obese group. In obese patients, the mean ISF concentrations of metronidazole were between 3 and 3.5mg/L throughout the measuring interval. Conclusions: During the time of surgery, cefazolin concentrations in plasma and ISF of subcutaneous tissue were lower in obese patients, but not clinically relevant. Regarding metronidazole, the respective differences were higher, and may influence dosing of metronidazole for perioperative prophylaxis in obese patients.

Item Type: Article
Uncontrolled Keywords: SURGICAL SITE INFECTION; MORBIDLY OBESE; ANTIMICROBIAL PROPHYLAXIS; SUBCUTANEOUS TISSUE; SURGERY; MICRODIALYSIS; PENETRATION; WOMEN; RISK; TIME;
Subjects: 600 Technology > 610 Medical sciences Medicine
600 Technology > 615 Pharmacy
Divisions: Medicine > Lehrstuhl für Anästhesiologie
Chemistry and Pharmacy > Institute of Pharmacy > Group Clinical Pharmacy (Dr. Dorn)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 29 Aug 2022 07:54
Last Modified: 29 Aug 2022 07:55
URI: https://pred.uni-regensburg.de/id/eprint/46410

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