Christoph Dorn1, David Petroff2,3, Melanie Stoelzel4, Martin G Kees5, Alexander Kratzer6, Arne Dietrich3,7, Charlotte Kloft8, Markus Zeitlinger9, Frieder Kees10, Hermann Wrigge3,11, Philipp Simon3,4. 1. Institute of Pharmacy, University of Regensburg, Regensburg, Germany. 2. Clinical Trial Centre, University of Leipzig, Leipzig, Germany. 3. Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany. 4. Department of Anaesthesiology and Intensive Care Medicine, University of Leipzig Medical Centre, Leipzig, Germany. 5. Department of Anaesthesiology, University Hospital Regensburg, Regensburg, Germany. 6. Hospital Pharmacy, University Hospital Regensburg, Regensburg, Germany. 7. Department of Surgery, University of Leipzig, Leipzig, Germany. 8. Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany. 9. Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. 10. Department of Pharmacology, University of Regensburg, Regensburg, Germany. 11. Department of Anaesthesiology, Intensive Care and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital Halle, Halle, Germany.
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 2 g cefazolin and 0.5 g metronidazole for perioperative prophylaxis. Plasma and microdialysate from subcutaneous tissue were sampled until 8 h after dosing. Drug concentrations were determined by HPLC-UV. Pharmacokinetic parameters were calculated non-compartmentally. RESULTS: In obese patients (BMI 39.5-69.3 kg/m2) compared with non-obese patients (BMI 18.7-29.8 kg/m2), mean Cmax of total cefazolin in plasma was lower (115 versus 174 mg/L) and Vss was higher (19.4 versus 14.2 L). The mean differences in t½ (2.7 versus 2.4 h), CL (5.14 versus 4.63 L/h) and AUC∞ (402 versus 450 mg·h/L) were not significant. The influence of obesity on the pharmacokinetics of metronidazole was similar (Cmax 8.99 versus 14.7 mg/L, Vss 73.9 versus 51.8 L, t½ 11.9 versus 9.1 h, CL 4.62 versus 4.13 L/h, AUC∞ 116 versus 127 mg·h/L). Regarding interstitial fluid (ISF), mean concentrations of cefazolin remained >4 mg/L until 6 h in both groups, and those of metronidazole up to 8 h in the non-obese group. In obese patients, the mean ISF concentrations of metronidazole were between 3 and 3.5 mg/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.
OBJECTIVES: To assess plasma and tissue pharmacokinetics of cefazolin and metronidazole in obesepatients undergoing bariatric surgery and non-obesepatients undergoing intra-abdominal surgery. PATIENTS AND METHODS: Fifteen obese and 15 non-obesepatients received an IV short infusion of 2 g cefazolin and 0.5 g metronidazole for perioperative prophylaxis. Plasma and microdialysate from subcutaneous tissue were sampled until 8 h after dosing. Drug concentrations were determined by HPLC-UV. Pharmacokinetic parameters were calculated non-compartmentally. RESULTS: In obesepatients (BMI 39.5-69.3 kg/m2) compared with non-obesepatients (BMI 18.7-29.8 kg/m2), mean Cmax of total cefazolin in plasma was lower (115 versus 174 mg/L) and Vss was higher (19.4 versus 14.2 L). The mean differences in t½ (2.7 versus 2.4 h), CL (5.14 versus 4.63 L/h) and AUC∞ (402 versus 450 mg·h/L) were not significant. The influence of obesity on the pharmacokinetics of metronidazole was similar (Cmax 8.99 versus 14.7 mg/L, Vss 73.9 versus 51.8 L, t½ 11.9 versus 9.1 h, CL 4.62 versus 4.13 L/h, AUC∞ 116 versus 127 mg·h/L). Regarding interstitial fluid (ISF), mean concentrations of cefazolin remained >4 mg/L until 6 h in both groups, and those of metronidazole up to 8 h in the non-obese group. In obesepatients, the mean ISF concentrations of metronidazole were between 3 and 3.5 mg/L throughout the measuring interval. CONCLUSIONS: During the time of surgery, cefazolin concentrations in plasma and ISF of subcutaneous tissue were lower in obesepatients, but not clinically relevant. Regarding metronidazole, the respective differences were higher, and may influence dosing of metronidazole for perioperative prophylaxis in obesepatients.
Authors: Rochelle L Ryan; Dwane Jackson; George Hopkins; Victoria Eley; Rebecca Christensen; Andre A J Van Zundert; Steven C Wallis; Jeffrey Lipman; Suzanne L Parker; Jason A Roberts Journal: Antimicrob Agents Chemother Date: 2022-06-28 Impact factor: 5.938
Authors: Christoph Dorn; David Petroff; Alexander Kratzer; Frieder Kees; Charlotte Kloft; Markus Zeitlinger; Hermann Wrigge; Philipp Simon Journal: Eur J Drug Metab Pharmacokinet Date: 2022-08-09 Impact factor: 2.569