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

Abstract

OBJECTIVES\nTo assess plasma and tissue pharmacokinetics of cefazolin and metronidazole in obese patients undergoing bariatric surgery and non-obese patients undergoing intra-abdominal surgery.\n\n\nPATIENTS AND METHODS\nFifteen obese and 15 non-obese patients received an IV short infusion of 2\u2009g cefazolin and 0.5\u2009g metronidazole for perioperative prophylaxis. Plasma and microdialysate from subcutaneous tissue were sampled until 8\u2009h after dosing. Drug concentrations were determined by HPLC-UV. Pharmacokinetic parameters were calculated non-compartmentally.\n\n\nRESULTS\nIn obese patients (BMI 39.5-69.3\u2009kg/m2) compared with non-obese patients (BMI 18.7-29.8\u2009kg/m2), mean Cmax of total cefazolin in plasma was lower (115 versus 174\u2009mg/L) and Vss was higher (19.4 versus 14.2\u2009L). The mean differences in t½ (2.7 versus 2.4\u2009h), CL (5.14 versus 4.63\u2009L/h) and AUC∞ (402 versus 450\u2009mg·h/L) were not significant. The influence of obesity on the pharmacokinetics of metronidazole was similar (Cmax 8.99 versus 14.7\u2009mg/L, Vss 73.9 versus 51.8\u2009L, t½ 11.9 versus 9.1\u2009h, CL 4.62 versus 4.13\u2009L/h, AUC∞ 116 versus 127\u2009mg·h/L). Regarding interstitial fluid (ISF), mean concentrations of cefazolin remained >4\u2009mg/L until 6\u2009h in both groups, and those of metronidazole up to 8\u2009h in the non-obese group. In obese patients, the mean ISF concentrations of metronidazole were between 3 and 3.5\u2009mg/L throughout the measuring interval.\n\n\nCONCLUSIONS\nDuring 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.