Cefazolin pharmacokinetics in morbidly obese patients following a prophylactic dose during weight reducing surgery.
Margreke J.E. Brill, Simone van Kralingen, Eric P.A. van Dongen, RenÚ J. Wiezer, Bert van Ramshorst, Catherijne A.J. Knibbe
St. Antonius Hospital, Nieuwegein, The Netherlands
Objectives: In this study we aimed to investigate the pharmacokinetics of cefazolin in morbidly obese patients undergoing weight reducing surgery.
Methods: At induction of anesthesia, morbidly obese patients received a dose of cefazolin 2 gram for the prevention of surgical site infections. Blood samples were drawn at T=0, 5, 10, 30, 60, 120, 180 and 240 min. after dosing and were analyzed using HPLC-UV. Cefazolin plasma concentrations were modelled using NONMEM VI and S-PLUS. A step-wise covariate analysis was performed to identify the influence of total body weight, lean body weight, ideal body weight, body mass index, age, sex, creatinine and bilirubin on the pharmacokinetics of cefazolin.
Results: Twenty morbidly obese patients with a median body weight of 144 kg (range 112 - 260 kg), a median age of 48 (range 22-59) and a median BMI of 51 kg/m2 (range 38-79 kg/m2) were included in the study. Cefazolin plasma concentrations were best described by a two-compartment model. Parameter estimates for clearance and central volume of distribution were 66.1 ml/min and 6.9 L, respectively. Total bodyweight proved the most predictive covariate for central volume of distribution (linearly centred) with inter-individual variability decreasing from 27.8% to 16.5% (p < 0.001). Age as a covariate for clearance implemented in an exponential manner further improved the model and reduced inter-individual variability for clearance from 42.1% to 34.9% (p < 0.05).
Conclusions: We developed a two-compartment pharmacokinetic model for cefazolin in morbidly obese patients in which total body weight and age proved to be the major determinants for respectively central volume of distribution and clearance of cefazolin. Plasma concentrations profiles in lean patients are awaited to confirm the currently observed covariate functions of clearance and central volume of distribution.