Dorn Christoph, Petroff David, Stoelzel Melanie, Kees Martin G, Kratzer Alexander, Dietrich Arne, Kloft Charlotte, Zeitlinger Markus, Kees Frieder, Wrigge Hermann, Simon Philipp
Institute of Pharmacy, University of Regensburg, Regensburg, Germany.
Clinical Trial Centre, University of Leipzig, Leipzig, Germany.
J Antimicrob Chemother. 2021 Jul 15;76(8):2114-2120. doi: 10.1093/jac/dkab143.
To assess plasma and tissue pharmacokinetics of cefazolin and metronidazole in obese patients undergoing bariatric surgery and non-obese patients undergoing intra-abdominal surgery.
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.
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.
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.
评估头孢唑林和甲硝唑在接受减肥手术的肥胖患者以及接受腹部手术的非肥胖患者中的血浆和组织药代动力学。
15名肥胖患者和15名非肥胖患者接受静脉短时间输注2g头孢唑林和0.5g甲硝唑用于围手术期预防。在给药后8小时内采集血浆和皮下组织的微透析液样本。通过高效液相色谱-紫外法测定药物浓度。非房室模型计算药代动力学参数。
与非肥胖患者（BMI 18.7-29.8kg/m²）相比，肥胖患者（BMI 39.5-69.3kg/m²）血浆中头孢唑林总量的平均Cmax较低（115对174mg/L），Vss较高（19.4对14.2L）。t½（2.7对2.4小时）、CL（5.14对4.63L/h）和AUC∞（402对450mg·h/L）的平均差异不显著。肥胖对甲硝唑药代动力学的影响相似（Cmax 8.99对14.7mg/L，Vss 73.9对51.8L，t½ 11.9对9.1小时，CL 4.62对4.13L/h，AUC∞ 116对127mg·h/L）。关于组织间液（ISF），两组中头孢唑林的平均浓度在6小时内均保持>4mg/L，非肥胖组中甲硝唑的平均浓度在8小时内保持该水平。在肥胖患者中，整个测量期间甲硝唑的平均ISF浓度在3至3.5mg/L之间。
在手术期间，肥胖患者皮下组织血浆和ISF中的头孢唑林浓度较低，但无临床相关性。关于甲硝唑，各自的差异较大，可能会影响肥胖患者围手术期预防中甲硝唑的给药剂量。
