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 ...
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.
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